Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
Substances
-
Antigens, CD
-
CD79 Antigens
-
Cd79a protein, mouse
-
Cd79b protein, mouse
-
DNA-Binding Proteins
-
Immunoglobulin Heavy Chains
-
Immunoglobulin Joining Region
-
Immunoglobulin Variable Region
-
Rag2 protein, mouse
-
Receptors, Antigen, B-Cell
-
V(D)J recombination activating protein 2
-
DNA Nucleotidyltransferases
-
VDJ Recombinases