Ig allotypic inclusion does not prevent B cell development or response.
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.
Velez
Maria-Gabriela
MG
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Kane
Melissa
M
Liu
Sucai
S
Gauld
Stephen B
SB
Cambier
John C
JC
Torres
Raul M
RM
Pelanda
Roberta
R
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*
D001323:Autoantibodies; C014609:IgK; D007126:Immunoglobulin Allotypes; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell