Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification.
Mice carrying transgenic rearranged V region genes in their IgH and Igkappa loci to encode an autoreactive specificity direct the emerging autoreactive progenitors into a pre-B cell compartment, in which their receptors are edited by secondary Vkappa-Jkappa rearrangements and RS recombination. Editing is an efficient process, because the mutant mice generate normal numbers of B cells. In a similar nonautoreactive transgenic strain, neither a pre-B cell compartment nor receptor editing was seen. Thus, the pre-B cell compartment may have evolved to edit the receptors of autoreactive cells and later been generally exploited for efficient antibody diversification through the invention of the pre-B cell receptor, mimicking an autoreactive antibody to direct the bulk of the progenitors into that compartment.
Pelanda
R
R
Institute for Genetics, University of Köln, Germany. pelanda@immunbio.mpg.de
Schwers
S
S
Sonoda
E
E
Torres
R M
RM
Nemazee
D
D
Rajewsky
K
K
D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006412:Hematopoietic Stem Cells; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000276:immunology; D051917:Leukosialin; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D012795:Sialoglycoproteins / Q000276:immunology
D015703:Antigens, CD; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D051917:Leukosialin; D011947:Receptors, Antigen, B-Cell; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D017493:Leukocyte Common Antigens