Macrophages and abnormal BCL-6 or c-MYC gene expression affect the resistance of peritoneal B cells to induction of hyporesponsiveness.

Our earlier results indicate that peritoneal B cells (PEB cells) were not hyporesponsive to in vitro crosslinking of the immunoglobulin (Ig) with a secondary anti-IgG reagent. In this study, the response of PEB cells was reduced by the same treatment given i.p. PEB cells were only sensitive to anti-IgM hyper-crosslinking in the presence of peritoneal macrophages. This sensitivity was partially reversed by anti-interferon-beta antibody. Elevated BCL-6 with c-MYC gene expression in NZB/W F1 splenic B cells after anti-IgM treatment correlated well with reduction of IgM secretion. On the contrary, PEB cells not sensitive to induction of hyporesponsiveness cause abnormal BCL-6/c-MYC gene expression after challenges. A bigger change of increased BCL-6 gene expression after anti-IgM treatment was seen in PEB cells than in splenic B cells. Higher BCL-2 gene expression in NZB/W splenic B cells than those in NZB/W PEB cells do not prevent hyporesponsiveness in the former. In conclusion, the relationship between BCL-6/c-MYC gene expression and IgM secretion in NZB/W F1 splenic B cells is similar to that of conventional B2 cells. Although PEB cells from wild type strain can be rendered hyporesponsive in vivo in the presence of macrophages, the resistance to hyporesponsiveness of challenged autoimmune NZB/W PEB cells in vivo is probably related to abnormal BCL-6/c-MYC gene expression. These combined findings suggest that autoimmune B1 cells violate the accepted paradigm for expression of differentiation-associated transcription factors in B2 cells.