Regulation of differentiation in CD5+ and conventional B cells. Sensitivity to LPS-induced differentiation and interferon-gamma-mediated inhibition of differentiation.

We have analyzed the response of conventional and CD5+ B cells to the opposing signals delivered by LPS and interferon-gamma (IFN-gamma). Cultured CD5+ B cells secrete more IgM than conventional B cells in response to low concentrations of LPS. This increase in LPS-induced IgM production is due to an increased precursor frequency of IgM-secreting cells in CD5+ B cells. The IgM-secreting clones derived from conventional splenic B cells or CD5+ peritoneal B cells exhibit similar kinetics of IgM secretion in response to LPS, and the amount of IgM produced per B cell clone was not higher in CD5+ B cells. Thus, the CD5+ B cell compartment produces more IgM in response to LPS because of increased activation of precursors at any given concentration of LPS. IFN-gamma inhibits low-dose LPS-driven IgM secretion in both conventional and CD5+ B cells. IFN-gamma mediates inhibition of IgM secretion by decreasing the precursor frequency of IgM-secreting conventional or CD5+ B cells by threefold. IFN-gamma also decreases the anti-ssDNA precursor frequency of LPS-driven splenic B cells from autoimmune NZB mice. This study documents an important role for IFN-gamma in the regulation of polyclonal B cell activation and suggests that loss of IFN-gamma activity may permit or promote excessive B cell activation.