Ig-alpha cytoplasmic truncation renders immature B cells more sensitive to antigen contact.
To study the function of Ig-alpha in the selection of autoreactive B cells, we have analyzed mb-1 cytoplasmic truncation mutant mice (mb-1delta(c)/delta(c)), which coexpress transgenes encoding hen egg lysozyme (HEL) and HEL-specific immunoglobulin. We demonstrate that in the presence of soluble HEL (sHEL) and dependent on the mb-1delta(c) mutation, most immature B cells bearing the HEL-specific Ig transgene undergo rearrangements of endogenous kappa light chains, resulting in loss of HEL specificity. Moreover, immature B cells from Ig-alpha mutant mice respond to BCR cross-linking with an exaggerated and prolonged calcium response and induction of protein tyrosine phosphorylation. Our data imply a negative signaling role for Ig-alpha in immature B cells.
Kraus
M
M
Department of Immunology, Institute for Genetics, University of Cologne, Germany. m.kraus@uni-koeln.de
Saijo
K
K
Torres
R M
RM
Rajewsky
K
K
D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017209:Apoptosis; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D051925:CD79 Antigens; D020013:Calcium Signaling / Q000276:immunology*; D017637:Clonal Deletion; D003433:Crosses, Genetic; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007152:Immunologic Capping; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic
D015703:Antigens, CD; D001324:Autoantigens; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D007145:Immunoglobulin kappa-Chains; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D009113:Muramidase