title: Surrogate light chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by marginal zone B cells.
abstract: Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Ren
authors.forename: Ola
authors.initials: O
authors.lastname: Grimsholm
authors.forename: Angelina I
authors.initials: AI
authors.lastname: Bernardi
authors.forename: Nina
authors.initials: N
authors.lastname: Höök
authors.forename: Anna
authors.initials: A
authors.lastname: Stern
authors.forename: Nicola
authors.initials: N
authors.lastname: Cavallini
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Mårtensson
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology*; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D018398:Homeodomain Proteins; D054444:Immunoglobulin Light Chains, Surrogate; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; C064658:RAG-1 protein
keywords: Autoantibodies; Autoimmunity; Light chain recombination; Marginal zone B cells; Pre-BCR