Transplanted Long-Term Cultured Pre-Bi Cells Expressing Calpastatin Are Resistant to B Cell Receptor–Induced Apoptosis

Long-term cultured pre-B cells are able to differentiate into immunoglobulin (Ig)M-positive B cells (IgM(+) cells) when transplanted into severe combined immunodeficient (SCID) mice. Based on previous studies, here we report the development of a reconstitution assay in nonobese diabetic/SCID (NOD/SCID) mice using pre-B cells, which allows us to study the role of calpains (calcium-activated endopeptidases) during B cell development as well as in B cell clonal deletion. Using this model, we show that calpastatin (the natural inhibitor of calpains) inhibits B cell receptor–induced apoptosis in IgM(+) cells derived from transplanted mice. We thus hypothesize an important function for calpain in sculpting the B cell repertoire.