Immune mechanisms leading to abnormal B cell selection and activation in New Zealand Black mice

Polyclonal B cell activation is a hallmark of the immune dysregulation in New Zealand Black (NZB) mice. We have previously shown that the splenic B cell activation is associated with increased CD80 expression. Here we show that abnormal expansions of CD80-expressing GC, CD5(+), marginal zone (MZ) precursor and MZ B cells produce this increase. To investigate the role of BCR engagement in the generation and activation of these populations, a non-self-reactive Ig Tg was introduced onto the NZB background. NZB Ig-Tg mice lacked Tg CD5(+) and peanut agglutinin(+) B cells, confirming the role of endogenous Ag in their selection. Although the increased proportion of MZ B cells was retained in NZB Ig-Tg mice, CD80 expression on these cells was reduced as compared to non-Tg NZB mice, suggesting a role for BCR engagement with endogenous Ag in their activation. Examination of CD40L-knockout NZB mice showed no difference in the abnormal activation or selection of the B cell populations, with the exception of GC cells, as compared to wild-type NZB mice. Thus, polyclonal B cell activation in NZB mice does not require CD40 engagement, but results, in part, from dysregulated BCR-specific mechanisms.