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 immunoglobuli n (Ig)M-positive B cells (IgM(+) cells) when transplanted into severe combi ned immunodeficient (SCID) mice. Based on previous studies, here we report the development of a reconstitution assay in nonobese diabetic/SCID (NOD/SC ID) 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 natu ral inhibitor of calpains) inhibits B cell receptor-induced apoptosis in Ig M(+) cells derived from transplanted mice. We thus hypothesize an important function for calpain in sculpting the B cell repertoire.