Bourke R. Maddox and David W. Scott

Immunology Department, American Red Cross Holland Laboratory, Rockville, MD 20855 USA

Received 03/29/96; Accepted 06/10/96; On-line 06/25/96

Two distinct subsets of B cells have been described in mice and humans: the conventional B cell, predominant in the spleen and lymph nodes, and the B1 (CD5⁺) cell, which comprises the majority of B cells in the peritoneum (>85%). B1 cells, which are prevalent early in ontogeny and possibly play a role in B-cell repertoire maturation, have been shown to express polyvalent, low affinity antibodies with self-reactivity (1) and have been linked to several autoimmune diseases (2). We (3,4) have previously shown that B1 cells are resistant to tolerance protocols involving crosslinking of sIgM that lead to hyporesponsiveness of conventional B cells. B1 cells, however, can be rendered hyporesponsive to LPS challenge by ionomycin or activation of protein kinase C with phorbol esters, for example, suggesting that B1 cells are defective in a calcium-dependent protein kinase C pathway (4, 5). In this communication, we compare the ability of B1 and conventional B cells to undergo programmed cell death (PCD) via apoptosis, and proliferation in response to sIgM crosslinking. To examine this, we used transgenic mice that either express rearranged receptors typical of the B1 repertoire, or rearranged receptors typical of con-ventional B cells; spleens from the B1 transgenic mice contain primarily cells of the B1/CD5⁺ type, unlike their normal counterparts. We have previously shown that the defect in signaling in murine B1 cells is not related to their location in vivo, but rather to differences in membrane signaling (4). It is these differences, and how they relate to PCD, that are of interest.