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Modulation of activation of polyclonal IgM, IgO and IgM anti-DNA antibodies by plasma fibronectin (Fn) was studied because in some autoimmune diseases there appears to be a correlation between the increased level of Fn in the affected tissues and increased polyclonal B-cell activation. Fn caused a dose-dependent polyclonal activation of IgM, IgG and IgM anti-DNA antibody-secreting cells in cultures of mouse splenocytes. Fn significantly inhibited the generation of polyclonal antibodies by Fn-binding stimulants and did not significantly change the generation of polyclonal antibodies by the stimulants that do not bind Fn. Plasmin or trypsin digestion of En abolished both the polyclonal activating properties of Fn and the inhibitory effects of En that were selective for the Fn-binding polyclonal activators. Digestion of Fn with trypsin also generated immunosuppressive Fn fragments that inhibited polyclonal activation by both En-binding and non-binding bacteria. Under our culture conditions Fn or Fn digests were not mitogenic and had no effect on the mitogenicity of Fn-binding and non-binding stimulants. These results indicate that Fn can act as a polyclonal activator and that it can also modulate lymphocyte activation induced by other activators. [ABSTRACT FROM AUTHOR]

We have compared the in vitro and in vivo mitogenic and polyclonal antibody (IgM-, IgG-, IgA- and anti-SRBC-secreting PFC) and autoantibody (IgM anti-ssDNA and anti-bromelin-treated mouse RBC-secreting PFC) responses to peptidogtycan (PG), LPS, protein A and PWM in homozygous xidor nu and normal mice. Our results demonstrated opposing effects of xid and nu on polyclonal B cell activation; in general, xid retarded and nu enhanced or did not change these responses. These effects, however, were greatly dependent on the in vitro or in vivo conditions of the stimulation and the type of polyclonal activator used and antibody assayed (isotype and specificity). In vitro, in xid mice, the numbers of all PFC assayed and proliferative responses were lower than in normal mice, whereas in nude mice the numbers of PFC were mostly unchanged, and proliferative responses were increased (PG, LPS) or decreased (protein A, PWM). The in vitro frequencies of autoantibody-secreting cells were similar (anti-DNA) in xid, nude and normal mice, or lower (anti-RBC) than normal in xid mice. In vivo, unstimulated xid mice had lower than normal numbers of IgM-, IgG- and autoantibody-secreting cells and higher numbers of IgA PFC, but in stimulated xid mice, the numbers of all Ig PFC were similar to normal, whereas anti-DNA and anti-RBC PFC were still depressed. The frequencies of anti-DNA and anti-RBC PFC were also lower than normal in xid mice in vivo. Nude mice in vivo had higher than normal numbers and frequencies of anti-DNA PFC and lower numbers of IgM and anti-SRBC PFC. These results indicate preferential retardation of autoantibody. secreting cells in xid mice in vivo and preferential enhancement of these cells in nude mice in vivo. Since in xid mice in vitro PG- and LPS-induced responses were similarly diminished, PG, like LPS, appears to primarily activate a late-maturing B cell subpopulation affected by the xid mutation. [ABSTRACT FROM AUTHOR]

We have compared the in vitro and in vivo mitogenic and polyclonal antibody (IgM-, IgG-, IgA- and anti-SRBC-secreting PFC) and autoantibody (IgM anti-ssDNA and anti-bromelin-treated mouse RBC-secreting PFC) responses to peptidoglycan (PG), LPS, protein A and PWM in homozygous xid or nu and normal mice. Our results demonstrated opposing effects of xid and nu on polyclonal B cell activation; in general, xid retarded and nu enhanced or did not change these responses. These effects, however, were greatly dependent on the in vitro or in vivo conditions of the stimulation and the type of polyclonal activator used and antibody assayed (isotype and specificity). In vitro, in xid mice, the numbers of all PFC assayed and proliferative responses were lower than in normal mice, whereas in nude mice the numbers of PFC were mostly unchanged, and proliferative responses were increased (PG, LPS) or decreased (protein A, PWM). The in vitro frequencies of autoantibody-secreting cells were similar (anti-DNA) in xid, nude and normal mice, or lower (anti-RBC) than normal in xid mice. In vivo, unstimulated xid mice had lower than normal numbers of IgM-, IgG- and autoantibody-secreting cells and higher numbers of IgA PFC, but in stimulated xid mice, the numbers of all Ig PFC were similar to normal, whereas anti-DNA and anti-RBC PFC were still depressed. The frequencies of anti-DNA and anti-RBC PFC were also lower than normal in xid mice in vivo. Nude mice in vivo had higher than normal numbers and frequencies of anti-DNA PFC and lower numbers of IgM and anti-SRBC PFC. These results indicate preferential retardation of autoantibody-secreting cells in xid mice in vivo and preferential enhancement of these cells in nude mice in vivo. Since in xid mice in vitro PG- and LPS-induced responses were similarly diminished, PG, like LPS, appears to primarily activate a late-maturing B cell subpopulation affected by the xid mutation.