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The primary immune response in vivo of 20 patients with selective IgA deficiency was studied and compared to controls. The primary cellular immune response tested by dinitrochlorobenzene (DNCB) was decreased in many patients. The primary humoral immune response was elicited by immunization with the test immunogen Helix pomatia haemocyanin (HPH). Using a direct ELISA technique antibodies against HPH of the IgA, IgG and IgM class were measured. Two weeks after immunization no response of IgA anti-HPH was seen except in three patients who showed a low but detectable antibody level. In spite of normal or even elevated serum IgG and IgM levels there was a significantly lower response of the IgG and IgM anti-HPH antibodies at 2 weeks after immunization as compared to the controls followed by a further decline at 6 weeks. We conclude that selective IgA deficiency is often accompanied by more general disturbances in humoral and cellular immunity to newly encountered antigens.

Concentrations of IgG2, IgG4 and IgE were low in 16, 24 and 20% of 25 persons with selective IgA deficiency. Fifty-two per cent had IgD concentrations below 5 iu/ml. Trends for association between any of these parameters and the presence of clinical symptoms were not significant. All patients, except one, had normal amounts of Ig-bearing lymphocytes in the blood. IgG1 antibodies against casein were increased in titre and frequency, whereas IgG4 antibodies were normal. Similar results were found in other sera from persons with selective IgA deficiency.

A panel of monoclonal antibodies (OKT3, 4, 6, 8, 10, 11) was used for the identification of T lymphocyte subpopulations in cell suspensions of human fetal liver, thymus, bone marrow and spleen. In liver suspensions of 8-16 week old fetuses and in bone marrow suspensions (12-20 weeks) less than 5% of lymphocytes reacted with either OKT3, 11, 4, 8 or 6, whereas the OKT10 antibody bound to, respectively, 35 and 86% of lymphocytes in these tissues. In liver suspensions of 17-20 week old fetuses, about 20% of lymphocytes carried either the T3, 11, 4 or 8 antigen and more than 60% of lymphocytes were OKT10+. The maturation stages in fetal thymus (11-20 weeks) are comparable to those in the post-natal thymus, with the exception that a substantial proportion of fetal thymocytes expresses the T3 and T6 antigen simultaneously. In the fetal spleen (12-20 weeks), 40% of lymphocytes reacts with OKT3. These OKT3+ spleen cells may be divided into two subsets expressing either the T4 antigen or the T8 antigen. These OKT3+/OKT4+ and OKT3+/OKT8+ lymphoid cells of the fetal spleen can be further subdivided into a T10+ and T10- subpopulation. These data suggest that T lymphoid precursor cells, reacting with either none of the monoclonal antibodies or only with OKT10, are generated in fetal liver (up till 16 weeks gestational age) and bone marrow. Further maturation takes place in the fetal thymus, but also to a certain extent in peripheral lymphoid organs such as the fetal spleen, as evidenced by the coexistence of a T3+/T10+ and T3+/T10- subpopulation in this organ.

Monoclonal antibodies (MoAbs) directed primarily against immature lymphoid cells (VIL-A1, BA-2, OKT10) or recognizing antigens associated with the B cell lineage (VIB-C5, OKI1) were used for the identification of lymphoid cells in liver, bone marrow, spleen and thymus of human fetuses between 8 and 20 weeks of gestational age. Many lymphocytes in liver, bone marrow and spleen reacted with the MoAbs used. In the fetal thymus, however, cells did not bind to the VIL-A1 and VIB-C5 MoAbs and only a few cells were BA-2+ or OKI1+. In the liver and bone marrow the VIL-A1, VIB-C5 and BA-2 MoAbs reacted almost exclusively with terminal deoxynucleotidyl transferase (TdT) containing cells, pre-B and B cells. TdT+ cells were present in liver, bone marrow and thymus, but not in the spleen. In liver and bone marrow the relative numbers of TdT+ cells decreased during gestation, in the thymus they increased. The antigenic make-up of the TdT+ cells in liver and bone marrow was comparable to that of pre-B and B cells in these organs: most of them reacted with VIL-A1, VIB-C5 and OKT10 MoAbs and many were BA-2+ and OKI1+. TdT+ cells in liver and bone marrow did not bind to T-cell-markers, i.e. OKT6 and WT-1. A few lymphoid cells in these organs contained TdT and mu heavy chains. TdT+ cells in the thymus had a completely different phenotype: most of them were OKT6+ and they did not react with the VIL-A1 and VIB-C5 MoAbs. These findings suggest that TdT+ cells in fetal liver and bone marrow are precursors of the B cell lineage, whereas those in the thymus probably belong to the T cell lineage. In the fetal spleen almost all B cells displayed the VIB-C5 and OKI1 antigens. At 12 weeks of gestation greater than 80% of splenic B cells were also VIL-A1+ and BA-2+; with ongoing gestation far less B cells in spleen expressed these antigens, however, indicating that these B cells are more mature than those in fetal liver and bone marrow, but still less mature than the B cells in postnatal blood and bone marrow, which do not display the VIL-A1 and BA-2 markers. These findings suggest that some further maturation of B cell stages takes place in the spleen during human fetal life.

Immunoglobulin levels of individual classes and IgG subclasses and the occurrence of homogeneous immunoglobulins--paraproteins--were studied longitudinally in the sera of three patients with the Wiskott-Aldrich syndrome; Common findings in all three patients were great variations in the immunoglobulin levels, restricted heterogeneity of the immunoglobulins, the frequent appearance of transient homogeneous immunoglobulins and the presence of serum antibodies against bovine milk proteins. A partial and selective deficiency involving mainly the T immune system is postulated as an explanation for these findings.