title: Ig allotypic inclusion does not prevent B cell development or response.
abstract: B cells expressing two different Ig kappa L chains (allotype included) have been occasionally observed. To determine frequency and function of these cells, we have analyzed gene-targeted mice that carry a human and a mouse Igk C region genes. Using different methodologies, we found that cells expressing two distinct kappa-chains were 1.4-3% of all B cells and that they were present in the follicular, marginal zone, and B1 mature B cell subsets. When stimulated in vitro with anti-IgM, dual kappa surface-positive cells underwent activation that manifested with cell proliferation and/or up-regulation of activation markers and similar to single kappa-expressing B cells. Yet, when activated by divalent reagents that bound only one of the two kappa-chains, dual kappa B cells responded suboptimally in vitro, most likely because of reduced Ag receptor cross-linking. Nonetheless, dual kappa B cells participated in a SRBC-specific immune response in vivo. Finally, we found that Ig allotype-included B cells that coexpress autoreactive and nonautoreactive Ag receptors were also capable of in vitro responses following BCR aggregation. In summary, our studies demonstrate that Ig kappa allotype-included B cells are present in the mouse mature B cell population and are responsive to BCR stimulation both in vitro and in vivo. Moreover, because in vitro activation in response to anti-IgM was also observed in cells coexpressing autoreactive and nonautoreactive Abs, our studies suggest a potential role of allotype-included B cells in both physiological and pathological immune responses.
authors.affiliation: Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
authors.forename: Maria-Gabriela
authors.initials: MG
authors.lastname: Velez
authors.forename: Melissa
authors.initials: M
authors.lastname: Kane
authors.forename: Sucai
authors.initials: S
authors.lastname: Liu
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gauld
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D007126:Immunoglobulin Allotypes; D007136:Immunoglobulins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C014609:IgK; D007126:Immunoglobulin Allotypes; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell