Allelic and isotypic light chain inclusion in peripheral B cells from anti-DNA antibody transgenic C57BL/6 and BALB/c mice.
Most mature B lymphocytes express one BCR L chain, kappa or lambda, but recent work has shown that there are exceptions in that some B lymphocytes express both kappa and lambda and some even bear two different kappa L chains. Using the anti-DNA H chain-transgenic mouse, 56R, we find that B cells with pre-existing autoreactivity are especially subject to L chain inclusion. Specifically, we show that isotypic and allelic inclusion enables autoreactive B cells to bypass central tolerance giving rise to B cells that retain dangerous features. One receptor in dual receptor B cells is an editor L chain, i.e., neutralizes or alters self-reactivity of the 56R H chain transgene. We compare the 56R mouse when on the C57/BL/6 background, a strain prone to autoimmunity, with that of 56R when on the BALB/c background, a strain that resists autoimmunity. In the B6.56R mouse, polyreactive B cells with dual L chain move to the follicular B cell compartment. Their localization in the follicular compartment may explain the ease with which B cells in the B6.56R differentiate into autoantibody-producing plasma cells. Likewise, in the BALB/c.56R mouse, dual L chain B cells are found in the follicular B cell compartment. Yet, the lack of autoantibody-producing plasma cells in the BALB/c.56R suggests that postfollicular tolerance checkpoints are intact. The Jkappa usage in dual kappa L chain B cells suggests increased receptor editing activity and is consistent with the expected distribution of Jkappa genes in our computational model for random selection of Jkappa.
Witsch
Esther J
EJ
Department of Pathology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA. esther.witsch@weizmann.ac.il
Bettelheim
Eldad
E
D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007127:Immunoglobulin Constant Regions / Q000096:biosynthesis / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017393:RNA Editing / Q000235:genetics* / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000974:Antibodies, Antinuclear; D007127:Immunoglobulin Constant Regions; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011947:Receptors, Antigen, B-Cell