A negative regulatory role for Ig-alpha during B cell development.
The development of B cells requires the expression of an antigen receptor at distinct points during maturation. The Ig-alpha/beta heterodimer signals for these receptors, and mice harboring a truncation of the Ig-alpha intracellular domain (mb-1(delta(c)/delta(c)) have severely reduced peripheral B cell numbers. Here we report that immature mb-1(delta(c)/delta(c) B cells are activated despite lacking a critical Ig-alpha-positive signaling motif. As a consequence of abnormal activation, transitional immature IgMhighIgDlow B cells are largely absent in mb-1delta(c)/delta(c) mutants, accounting for the paucity of mature B cells. Thus, Ig-alpha cytoplasmic tail truncation yields an antigen receptor complex on immature B cells that signals constitutively. These data illustrate a role for Ig-alpha in negatively regulating antigen receptor signaling during B cell development.
Torres
R M
RM
Basel Institute for Immunology, Switzerland. torres@bii.ch
Hafen
K
K
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology*; D051940:B7-2 Antigen; D051925:CD79 Antigens; D019281:Dimerization; D007075:Immunoglobulin M / Q000096:biosynthesis; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology / Q000196:embryology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013728:Terminator Regions, Genetic
D015703:Antigens, CD; D051940:B7-2 Antigen; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; C497965:Cd86 protein, mouse; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases