Opposing effects of <em>xid</em> and <em>nu</em> mutations on proliferative and polyclonal antibody and autoantibody responses to peptidoglycan, LPS, protein A and PWM.

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]