Igkappa allelic inclusion is a consequence of receptor editing.
The discovery of lymphocytes bearing two light chains in mice carrying self-reactive antibody transgenes has challenged the "one lymphocyte-one antibody" rule. However, the extent and nature of allelically included cells in normal mice is unknown. We show that 10% of mature B cells coexpress both Igkappa alleles. These cells are not the result of failure in allelic exclusion per se, but arise through receptor editing. We find that under physiological conditions, editing occurs both by deletion and by inclusion with equal probability. In addition, we demonstrate that B lymphocytes carrying two B-cell receptors are recruited to germinal center reactions, and thus fully participate in humoral immune responses. Our data measure the scope of allelic inclusion and provide a mechanism whereby autoreactive B cells might "escape" central tolerance.
Casellas
Rafael
R
Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zhang
Qingzhao
Q
Zheng
Nai-Ying
NY
Mathias
Melissa D
MD
Smith
Kenneth
K
Wilson
Patrick C
PC
D000483:Alleles; D000818:Animals; D000916:Antibody Diversity; D000940:Antigenic Variation; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D066298:In Vitro Techniques; D051379:Mice; D018448:Models, Immunological; D017393:RNA Editing; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D017634:Self Tolerance
D017931:DNA Primers; D007145:Immunoglobulin kappa-Chains; D011947:Receptors, Antigen, B-Cell