B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta

• Published in: The Journal of immunology (1950) Vol. 169; no. 2; pp. 865 - 872
• Main Authors: Pelanda, Roberta, Braun, Uschi, Hobeika, Elias, Nussenzweig, Michel C, Reth, Michael
• Format: Journal Article
• Language: English
• Published: United States 15.07.2002
• Subjects: Animals; Antibody Diversity - genetics; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - physiology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; CD79 Antigens; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Survival - genetics; Cell Survival - immunology; Crosses, Genetic; DNA Nucleotidyltransferases - deficiency; DNA Nucleotidyltransferases - genetics; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Joining Region - biosynthesis; Immunoglobulin Joining Region - genetics; Immunoglobulin Variable Region - biosynthesis; Immunoglobulin Variable Region - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, B-Cell - biosynthesis; Receptors, Antigen, B-Cell - deficiency; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - physiology; Stem Cells - immunology; Stem Cells - metabolism; Stem Cells - pathology; VDJ Recombinases
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.2.865

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.