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.
Ruiz-Vela
A
A
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco UAM, E-28049 Madrid, Spain. aruiz@cnb.uam.es
Serrano
F
F
González
M A
MA
Abad
J L
JL
Bernad
A
A
Maki
M
M
Martínez-A
C
C
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D017637:Clonal Deletion; D015870:Gene Expression; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008954:Models, Biological; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D007075:Immunoglobulin M; D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; C033668:calpastatin; D002154:Calpain