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Harper D, Gollackner B, Xu Y, Calderhead D, Ryan D, Li W, Chang J, Wu C, Moran K, Latinne D, Bazin H, White-Scharf ME, Cooper DKC, Awwad M. In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb). Xenotransplantation 2004; 11: 78–90. © Blackwell Munksgaard, 2004 Natural antibodies (Abs), predominately anti-Gal α1–3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naïve baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of immunoglobulin E (IgE) in the late phase reaction (LPR) of murine experimental asthma. Our model consisted of an implant of DNP-conjugated, heat-coagulated hen's egg white (DNP-EWI), followed 14 days later by an intratracheal challenge with aggregated DNP-ovalbumin. Airway inflammation was analyzed 48 h after challenge and compared with a similarly immunized group of mice with highly suppressed humoral response due to anti- μ and anti- δ antibody treatment. Total number of cells in the bronchoalveolar lavage (BAL) (with predominance of eosinophils) and EPO activity in the lung homogenate were increased in the DNP-EWI-immunized group compared with immunosuppressed or nonimmunized mice. However, the cellular infiltration and EPO activity observed in the immunosuppressed group were still significantly above those obtained in the nonimmunized group, indicating that inhibition of antibody production did not completely prevent the inflammatory manifestations in BAL and lung. Airway hyperresponsiveness to methacoline was obtained in DNP-EWI-immunized mice, but the respiratory mechanical parameters returned to normal levels in the immunosuppressed group. When these mice were reconstituted with monoclonal anti-DNP antibodies, only IgE, but not IgG1, restored lung inflammation and decreased the conductance of the respiratory system, therefore, increasing hyperresponsiveness. These results indicate that antibodies are not essential for induction of LPR in the lung. However, IgE enhances pulmonary inflammation and hyperresponsiveness. [ABSTRACT FROM AUTHOR]

The B-cell development in a group of rats was suppressed for the first 45 days of life by serial administration of rabbit anti-rat IgM and IgD antibody. Total or near total suppression of B lymphopoiesis was achieved. At 45 days, suppression was stopped by injection of IgM and IgD rat paraproteins. The sequence of B-cell and plasma cell development following suppression was assessed by immunohistological analysis of spleen lymph nodes and small intestinal lamina propria. The main findings are listed below. (i) Complete reconstitution of B-cell numbers occurs within 8 days, at which stage germinal centres are also present. (ii) B lymphopoiesis in the red pulp of the spleen differs from that reported for bone marrow. Cells develop expressing surface sIgM and sIgM with IgA, but not sIgD. (iii) sIgD-positive cells first appear in splenic follicles 2 days after stopping suppression, but their appearance in lymph nodes is delayed until after 3 days. At this stage, sIgD-positive cells become apparent in the splenic red pulp. (iv) IgM plasma cells appear from day 4. IgA plasma cells in the gut appear in small numbers at day 6, and gradually increase to normal numbers by day 14. (v) sIgG2c expression in the splenic marginal zone did not approach normal levels, even 2 weeks after suppression was stopped. [ABSTRACT FROM AUTHOR]

Inbred BN-rats were immunized at different ages with a standardized amount of ovalbumin and Al(OH)3. The specific IgE antibody response and total serum IgE levels were significantly influenced by age. The IgE antibody response increased to a maximum in 2-month-old rats and decreased progressively at a more advanced age. Total serum IgE levels increased progressively from the age of 1 month to the age of 5 months and decreased again at the age of one year. [ABSTRACT FROM AUTHOR]

Strain differences in total serum IgE levels and IgE antibody responses to various amounts of antigen were studied in rats. Five inbred strains (BN, Wistar R/A, DA, LEW, PVG), (Wistar R/A × RN) F1 and (LEW × BN) Fl hybrids were immunized twice at an interval of 28 days by intraperitoneal injection of 10 ng, 100 ng, 1 µg, 10 µg, 100 µg or 1 mg ovalbumin and 1 mg Al(OH)3 in a volume of 0.5 ml. Total serum IgE and IgE antibody levels were followed. Both parameters were measured with a solid phase radioimmunoassay. A significant difference was observed in total IgE levels between the different strains. The IgE antibody response depended both on the strain and on the amount of antigen used for immunization. There was an optimal antigen dose for IgE antibody formation, differing from strain to strain. F1 hybrids had total IgE levels and IgE responses Intermediary between those of the two parent strains. A good correlation existed between the total serum IgE level before immunization and the magnitude of the optimum IgE antibody responses in the different strains. These results suggest that there may be a genetic influence on both parameters, the total IgE level and the specific IgE antibody response. The IgE antibody response is also dependent on the dose of antigen. [ABSTRACT FROM AUTHOR]

Investigates serum immunoglobulin E (IgE) levels after infection by Schistosoma mansoni in various strains of rats. Use of radioimmunoassay in measuring serum IgE levels in four strains of rats, before and after infection of Schistosoma mansoni; Observation of differences in basal IgE levels, depending on the strain considered; Identification of the persistence of high IgE levels as a characteristic feature of IgE production in rat schistosomiasis.

Reaginic antibody synthesis following parenteral and/or oral administration of ovalbumin and Bordetella pertussis organisms as adjuvant has been evaluated in LOU/M/Wsl inbred rats. These rats are able to produce high reaginic antibody serum levels after intraperitoneal injection of this antigen. Primary oral administration of ovalbumin doses between 10 and 100 mg with Bordetella pertussis organisms given as adjuvant by the intraperitoneal or the oral route led to characteristic reaginic responses. Secondary reaginic responses were obtained by oral administration of ovalbumin without any adjuvant in animals sensitized by the oral or the intraperitoneal route. A hundred micrograms of ovalbumin was enough to induce reaginic responses but more constant and higher reaginic levels were obtained with a 50 mg dose in the experimental model employed. [ABSTRACT FROM AUTHOR]

The inbred LOU/Wsl rat strain presents a high incidence of spontaneous ileocoecal immunocytoma which secrete monoclonal immunoglobulins. These tumours are transplantable in histocompatible animals and their secreting properties are maintained over many passages. A screening of monoclonal immunoglobulins secreted by 250 such tumours revealed sixty-three proteins which shared class-specific determinants, physico-chemical features and biological properties different from those of rat IgM, IgA, IgG1, IgG2a, IgG2b and IgG2c classes, and characteristic of proteins of the IgE class. [ABSTRACT FROM AUTHOR]

Rat spleen cells were stimulated with pokeweed mitogen (PWM) and the IgM and IgE responses were assessed. An enrichment of the cell suspension with IgE-bearing cells before stimulation resulted in an increase in the number of IgE-secreting cells. A decrease of the number of IgE-secreting cells was found after depletion of IgE- or IgM-bearing cells, but not those bearing IgD molecules on their membranes, before stimulation. Moreover, the stimulation of membrane IgE on B cells with anti-IgE antibodies was shown to increase the number of IgE-secreting cells after PWM-induced differentiation in vitro. In vivo, it was also observed that a single injection of anti-IgE antibodies can induce the differentiation of IgE-secreting cells. These results demonstrate the presence of IgE+-IgM+-IgD- B cells in the rat that are responsive to PWM-induced differentiation into IgE-secreting cells. They indicate a pre-commitment of these cells at a stage where they still express IgM on their surface, IgE molecules on the cell membranes play a role in their differentiation. [ABSTRACT FROM AUTHOR]

Functional characteristics of cultured bone marrow-derived rat mast cells (BMMC) were studied. BMMC were shown to release in a time- and dose-dependent fashion the mucosal mast cell (MMC)-specific enzyme, rat mast cell protease II (RMCPII), following IgE-mediated activation in vitro. RMCPII release was temporally associated with that of the mast cell granule-derived enzyme, β-hexosaminidase (β-hex). Release of the pre-formed granule constituents, RMCPII and β-hex, was associated with the generation of the membrane-derived lipid mediator, leukotriene C4 (LTC4) and, in older cultures, substantial amounts were generated (25.2 ng/106 BMMC). Absolute amounts of RMCPII, β-hex and LTC4 released were dependent upon the age of the BMMC. These results extend our previous observations on the staining properties and protease content of rat BMMC and provide evidence that these cells are functionally, as well as histochemically, analogous to the MMC subset, which is so prominent during intestinal nematode infections in rats. [ABSTRACT FROM AUTHOR]

Among the rat antibodies tested in this study, monoclonals of IgG2a isotype were the best, IgGI and IgG2b being also effective, for induction of K-cell-mediated cytotoxicity of relevant nucleated target cells by rat effectors (Nude spleen cells). The single rat monoclonal IgE tested was also active. Rat antibodies of IgM and IgA classes of immunoglobulins were not active in that system. IgG2c and IgD monoclonals were not tested. Using the same pannel of reagents, cytotoxicity mediated by human K cells (peripheral blood mononuclear cells) was only induced by the IgG2b class of rat monoclonals. [ABSTRACT FROM AUTHOR]

The fate of allogeneic lymphocytes (AO or DA) transferred to non-immune PVG recipients was studied in the light of previous evidence (Heslop & McNeilage, 1983; Rolstad & Ford, 1983) that allogeneic lymphocytes can be rapidly destroyed in certain strain combinations of rats and mice by a mechanism that is distinct from either T-cell mediated immunity or an alloantibody response. AO lymphocytes injected into PVG recipients were discriminated from syngeneic lymphocytes within 15-30 min of i.v. injection, as testified by the excess release of 51Crk into the lymph plasma of the recipient. The following experiments were intended to distinguish between natural antibody and natural killer (NK) cells as the mechanism responsible for the allogeneic lymphocyte cytotoxicity (ALC) displayed by PVG rats. Nude rats treated from birth with anti-μchain serum and shown to be lacking B and T lymphocytes, as well as being profoundly deficient in immunoglobulin, displayed more aggressive ALC than did control nude rats which, in turn, showed stronger ALe than did euthymic rats. Serum from PVG nude rats exerted no inhibitory or destructive effect on allogeneic lymphocytes in an antibody dependent cellular cytotoxicity system, an assay of graft-versus-host activity, or when injected into 3-4-week-old PVG rats which had not yet developed ALC. Treatment of nude rats with anti-asialo GM1 antiserum depressed ALe and NK activity in parallel, thus adding to a wide range of circumstances in which ALC and NK activity are closely correlated. In conclusion, ALC is implemented by a non-adaptive, cell-mediated mechanism independent of immunoglobulin, but the precise identity of the effector cell in the recipients' lymphatic tissues remains to be settled. [ABSTRACT FROM AUTHOR]

Examines the formation of antibodies to the respective idiotypes of myeloma proteins produced by MOPC plasmocytoma tumours of BALB/c origin. Description of the biological characteristics and morphology of the IR202 transplantable immunocytoma tumour in rats; Presentation of the 202M protein molecules on the macrophage surface; Development of antibodies specific to individual antigenic determinant of the monoclonal IgM.

The influence of the thymus and the possible requirement for surface immunoglobulin expression for the development of K and NK activity were assessed in rats. This species was chosen in preference to mice as they show good levels of K-cell activity. Studies were carried out in athymic (rnu/rnu) rats some of which were treated from birth with rabbit anti-rat IgM antibody to suppress B-cell development. The results indicate that normal levels of both K and NK activity develop in the spleens of 6-8-week-old athymic rats, which do not contain cells expressing surface membrane immunoglobulin. While K and NK cells show characteristics of the lymphoid lineage, neither the thymus nor surface membrane immunoglobulin expression appears to be required for development of normal levels of these cytolytic activities. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that IgE molecules are heterogeneous with respect to ability to compete with IgE myeloma for sensitization of histamine release from chopped human lung and ability to passively sensitize human basophils for antigen-induced histamine release. These observations prompted further investigation of the possibility that there exists a functional heterogeneity in the IgE molecules with respect to mast-cell binding properties. Using eight different purified rat IgE myeloma proteins, we found that they differ in their ability to inhibit the passive cutaneous anaphylaxis (PCA) reaction of mouse reaginic antisera. This suggests that IgE molecules differ in their ability to bind to mast cell receptors. Since maximal inhibition of different mouse reaginic antisera and mouse IgE hybridomas is achieved with different IgE myelomas, there may exist a functional heterogeneity in mast-cell binding receptors as well. [ABSTRACT FROM AUTHOR]

Antibodies against the dinitroaminophenyl (DNAP) haptenic group were raised in outbred CFY rats using HSA or LPS as carrier. Antibodies isolated by immunoadsorbent techniques were resolved into fractions representing distinct isotypes, and the resulting fractions were tested for avidity. Subclass IgG2a was found to contain antibodies of an avidity index lower than those of other IgG subclasses or IgM. IgG2a was the only isotype detected when DNAP-LPS was used for immunization. Complexes containing defined isotypes were compared for their capacity to activate homologous complement, IgG1 type antibody-containing complexes displayed a low complement activating capacity compared with those containing IgG2b, IgG2c or IgG2a. The latter subclass when complexed with antigen can thus induce complement-dependent processes in spite of a low avidity. Insoluble complexes of IgG antibodies were rapidly solubilized in rat serum (CRA phenomenon), except those containing predominantly IgG2c. [ABSTRACT FROM AUTHOR]

Parasite specific IgE antibodies in rats infected with Schistosoma mansoni were measured by passive cutaneous anaphylaxis (PCA) reactions and by the technique of immuno-adsorption. Two strains, one a low IgE producer (Fischer rats) and the other a high IgE producer (Hooded-Lister rats) were studied. In Fischer rats, a time course study of the occurrence of IgE antibodies and resistance to reinfection was made. Parasite specific IgE levels measured by immuno-adsorption were much lower than total IgE levels and a similar percentage of specific IgE (about 8%) was found in the two strains. IgE antibodies were maximum at day 30 and day 60 after infection; however, a third peak at day 90 was observed only in Fischer rats. Some discrepancies between results obtained by PCA and immunosorbent techniques have been observed, which could be explained by differences in the affinity of IgE antibodies during infection or by the presence of total IgE in the PCA assay. There was a close parallelism between specific IgE antibodies levels and the course of immunity in Fischer rats. This parallelism supports the view that IgE could play a pre-eminent role in protective immunity in rat schistosomiasis. [ABSTRACT FROM AUTHOR]

It has recently been established that mast cells display functional heterogeneity. The question then arises whether the IgE-type of antibody, which avidly binds to and thereby sensitizes mast cells and basophils for allergen-induced release of mediators, also expresses functional heterogeneity. In the present article we bring together several experimental observations, mainly from the rat system, which are difficult to explain unless one postulates that mast cell/basophil-sensitizing antibodies of the IgE-type are heterogeneous in their cell-binding properties. [ABSTRACT FROM AUTHOR]

PVG rats given injections of 1 μ ovalbumin (OA) together with 10 mg Silica gel failed to provide serosal mast cells or lung tissue with the capacity to release histamine on in vitro challenge with the antigen. However, if such animals were injected i.p. with 100 mg of alum (without any further antigen addition) 3-9 weeks after the primary antigen injection, their mast cells and lung tissue showed a clear-cut capacity to respond in vitro, when examined 1 week after the alum injection. Injection of only 15 mg alum did not induce such a response capacity. The fading of the reactivity induced by an alum injection could be prevented by a repeated injection of the adjuvant alone. Pretreatment of the rats with cyclophosphamide (33 mg/kg) 2 days before the primary antigen injection did not affect the response capacity induced by a booster injection 3 weeks later. S.C. injection of alum also precepitated response capacity in animals primed by i.p. injection of antigen and Silica gel. The anaphylactic response capacity induced by injection(s) of alum was generally accompanied by increased levels of OA-IgE and especially OA-IgG2a antibody; however, a clear-cut correlation between either serosal mast cell or lung tissue response capacity and serum OA-IgE or IgG2a antibody titer could not be demonstrated. These data show that in primed animals, which do not express allergic response capacity, such a capacity can be induced by injecting adjuvant alone, even several weeks after the primary antigen injection. [ABSTRACT FROM AUTHOR]

Bordetella pertussis organisms, with or without a small dose of alumhydroxide, enhance in rats the production of IgE antibodies to an unrelated antigen, even if this antigen has been administered 6 weeks beforehand. This non-specific enhancement of IgE antibodies is accompanied by a substantial rise in total serum IgE and by the production of IgE antibodies to B. pertussis. The effect of B. pertussis on IgE synthesis is dose-dependent. No effect of B. pertussis on IgE production can be observed in nude rats. [ABSTRACT FROM AUTHOR]

In this study, we have analysed in mice the effects on the immune response of in vivo treatment with different rat monoclonal antibodies (MoAb) against IgM and IgD. Although the effects of IgD cross-linking have been studied already, no attempt has been made to characterize the effects of in vivo IgM crosslinking, probably because of the higher IgM serum levels compared to IgD. We have used a panel of nine monoclonal rat anti-mouse IgM and three anti-IgD antibodies and we have characterized their isotypes, avidities, immunoglobulin (Ig) cross-linking and internalization abilities. Our results show that injection of mice with some rat MoAb against IgM led to an important decrease of IgM serum level and internalization of membrane IgM (mIgM) on almost all B cells. Similarly, treatment with a high-avidity anti-IgD antibody induced disappearance of mIgD on B cells. Treatment with rat MoAb against IgM or IgD led to a synthesis of specific antibodies and there was a direct relationship between the Ig internalization abilities of rat MoAb and the induction of specific antibody production. Finally, treatment with a high-avidity rat MoAb against IgD induced a polyclonal IgE and IgG1 secretion. The significance of these results on mIg receptor functions is discussed. [ABSTRACT FROM AUTHOR]

In the present study the clearance kinetics and tissue distribution of aggregated 125I-labelled monoclonal rat IgA ([125I] AlgA) of different sizes were studied in rats. Soluble [125I]AlgA disappeared from the circulation in a biphasic manner with an initial rapid distribution half-life (T1) and a second slower half-life (T2). T2 was directly related to the size of the aggregates. High molecular weight [125I]AlgA, containing 10-12 IgA molecules per aggregate ([IgA] 10-12). was cleared much faster than low molecular weight aggregates. The main site of clearance was the liver. The larger the size of the AlgA, the more degradation products were found in the circulation. After injection of [IgA] 10-12, non-parenchymal cells (NPC) contained three times moreradioactivity than parenchymal cells (PC) (NPC:PC ratio 3.06 &plsmn;0.96 ) Ratios of 0.82 &plusmn 0.03 and 0.62 ±0.12 were observed when [IgA] 5-6, and [IgA] 2 were injected respectively, suggesting a greater role for Kupffer cells in the clearance of large-sized IgA aggregates. Kupffer cells were shown to be the main cells for localization of large-sized AlgA established by immunohistochemical staining on liver cryostat sections. [ABSTRACT FROM AUTHOR]

Monomcric(m-) and polymeric (p-) anti-DNP monoclonal (MC) rat IgA antibodies (Ab) were tested for precipitation with DNP-bovine serum albumin (DNP-BSA) and C3 conversion in rat serum, with rat MC anti-DNP IgG2b used as reference. At equivalence, p-IgA rapidly precipitated DNP-BSA, with little antigen (Ag) left in the supernatant. In contrast, m-IgA at five-fold higher concentration precipitated Ag very slowly, with <50% of Ag precipitated at equivalence. The Ag/Ab weight ratio at equivalence was 0.13 for both m- and p-IgA, but the molar ratio was 0.3 for m-IgA and close to 1.0 for p-IgA, suggesting a higher avidity of p-IgA, Rat C3 conversion by rat IgA immune precipitates (IP) was about 20% with m-IgA and 40% with p-IgA. EGTA did not significantly affect these figures. Therefore, rat MC IgA IP activated the rat alternative C pathway. Neither rat nor mouse IgA anti-DNP IP activated C3 in normal human serum. [ABSTRACT FROM AUTHOR]

Improved experimental conditions are described for the treatment of mice with anti-IgM antibody, which subsequently lead to B-cell deficiency and agammaglobulinaemia. Antibody transmitted via maternal milk alone was found to be more efficient in inducing suppression of serum immunoglobulin isotypes than prenatal transmission or postnatal intraperitoneal injections alone. However, the combined treatment by all three routes of exposure to anti-IgM resulted in total B-cell suppression associated with undetectable levels of all serum immunoglobulin isotypes. Furthermore, suppression of B-cell generation was also achieved with a rat monoclonal μ-specific antibody. The possibility of generating agammaglobulinaemic mice may be useful for investigating the influence of B cells on the generation of T-cell reactivities, and for analysing the effects of monoclonal antibodies in the absence of interfering serum immunoglobulin. [ABSTRACT FROM AUTHOR]

BALB/c conventional mice carrying plasma cell tumour grafts which secrete IgA do not, in contrast to normal mice, experience any decline in their serum IgA levels following wholebody irradiation by 900 R, provided the tumours themselves are protected from X-ray damage. Germ-free Swiss mice whose serum IgA levels had been raised to near-normal values by a transfusion with normal mouse serum, did not show any selective decline in the serum IgA concentration following whole-body-exposure to 2000 R, in contrast to conventional adult mice in which this class of immunoglobulin is severely and selectively depressed by a similar treatment. Nor did germ-free transfused mice excrete abnormally high quantities of IgA into their intestinal fluids. It is concluded that the previously described selective fall in serum IgA levels following irradiation does not occur when the source supplying IgA to the serum pool is protected from the action of X-rays. Conversely, this metabolic disturbance cannot be explained by any specific increase of catabolism or intestinal loss of this serum immunoglobulin. [ABSTRACT FROM AUTHOR]

It was demonstrated in earlier publications that the acute and selective fall in serum IgA levels in irradiated mice was due to a specific failure to renew the plasma pool of this immunoglobulin. In the present work, it is shown that irradiation causes some reduction in the rate of biosynthesis of IgA, but that this phenomenon only partly accounts for the observed disturbance in the metabolism of IgA. This conclusion is based both on direct measurements on the rate of biosynthesis in vitro of IgA by the isolated small bowel wall of irradiated and normal C3H mice, and on immunohistologicaI studies and plasma cell counts on the gut, spleen and lymph nodes of these animals. On the other hand, it is shown that irradiated mice continue to excrete approximately normal amounts of IgA into their intestinal contents. The conclusion is that irradiation of the gut causes a rechannelling in the output of IgA synthesized by the plasma cells of the lamina propria, the major part being diverted to the intestinal lumen instead of being fed into the circulating pool of serum IgA. [ABSTRACT FROM AUTHOR]

Adult C3H mice were irradiated by 700 r in toto or with the gut shielded. In similar experiments the gut alone was irradiated. The earlier observation of a selective and profound decrease of serum IgA, moderate decrease in IgG1 and IgG2, and little change in IgM, was confirmed for the animals irradiated without protection of the gut. Similar effects were found when the gut alone was irradiated, whereas whole-body irradiation with the gut shielded caused only little change in the different serum immunoglobulins. Hence the characteristic responses of the serum irnmunoglobulins appeared to result from X-ray damage to the intestine. From this and a preceding study it was hypothesized that such damage resulted in moderate losses of IgG from the blood stream into the intestinal lumen, but that the selective and severe depression of serum IgA was mostly due to the escape, through the damaged epithelium, of that portion of the secretion from intestinal plasma cells which normally would have joined the blood stream. [ABSTRACT FROM AUTHOR]

The catabolism of the different classes of immunoglobulins (IG) of normal and irradiated mice was studied. A lethal dose of X-rays brought about no significant alterations in the catabolic rates of IgM and IgA, which kept to a time of about 12 hours. Contrariwise, the IgG (IgG1, IgG2a and IgG2b) displayed a distinctly accelerated catabolism in the irradiated mice, the half-life of these Ig's being reduced by approximately one-half. We propose an interpretation of this phenomenon, based, on one hand, on the great radiosensitivity of the intestinal epithelium and, on the other hand, on the mode of catabolism of IgM and IgA which appears to be different from that of IgG. [ABSTRACT FROM AUTHOR]