B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta.
Ig-alpha and Ig-beta mediate surface expression and signaling of diverse B cell receptor complexes on precursor, immature, and mature B cells. Their expression begins before that of the Ig chains in early progenitor B cells. In this study, we describe the generation of Ig-alpha-deficient mice and their comparative analysis to mice deficient for Ig-beta, the membrane-IgM, and recombination-activating gene 2 to determine the requirement of Ig-alpha and Ig-beta in survival and differentiation of pro-B cells. We find that in the absence of Ig-alpha, B cell development does not progress beyond the progenitor stage, similar to what is observed in humans lacking this molecule. However, neither in Ig-alpha- nor in Ig-beta-deficient mice are pro-B cells impaired in V(D)J recombination, in the expression of intracellular Ig micro-chains, or in surviving in the bone marrow microenvironment. Finally, Ig-alpha and Ig-beta are not redundant in their putative function, as pro-B cells from Ig-alpha and Ig-beta double-deficient mice are similar to those from single-deficient animals in every aspect analyzed.
Pelanda
Roberta
R
Biologie III, University of Freiburg and Max-Planck-Institute for Immunobiology, Freiburg, Germany. pelandar@njc.org
Braun
Uschi
U
Hobeika
Elias
E
Nussenzweig
Michel C
MC
Reth
Michael
M
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051925:CD79 Antigens; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004254:DNA Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045567:VDJ Recombinases
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases