Direct Reduction of Antigen Receptor Expression in Polyclonal B Cell Populations Developing In Vivo Results in Light Chain Receptor Editing

• Published in: The Journal of immunology (1950) Vol. 188; no. 1; pp. 47 - 56
• Main Authors: Shen, Shixue, Manser, Tim
• Format: Journal Article
• Language: English
• Published: England 01.01.2012
• Subjects: Animals; Cell Line; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Immunoglobulin kappa-Chains - biosynthesis; Immunoglobulin kappa-Chains - genetics; Immunoglobulin kappa-Chains - immunology; Immunoglobulin lambda-Chains - biosynthesis; Immunoglobulin lambda-Chains - genetics; Immunoglobulin lambda-Chains - immunology; Mice; Receptors, Antigen, B-Cell - biosynthesis; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - immunology; RNA Editing - genetics; RNA Editing - immunology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Messenger - immunology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1102109

Secondary Ab V region gene segment rearrangement, termed receptor editing, is a major mechanism contributing to B lymphocyte self-tolerance. However, the parameters that determine whether a B cell undergoes editing are a current subject of debate. We tested the role that the level of BCR expression plays in the regulation of receptor editing in a polyclonal population of B cells differentiating in vivo. Expression of a short hairpin RNA for κ L chain RNA in B cells resulted in reduction in levels of this RNA and surface BCRs. Strikingly, fully mature and functional B cells that developed in vivo and efficiently expressed the short hairpin RNA predominantly expressed BCRs containing λ light chains. This shift in L chain repertoire was accompanied by inhibition of development, increased Rag gene expression, and increased λ V gene segment-cleavage events at the immature B cell stage. These data demonstrated that reducing the translation of BCRs that are members of the natural repertoire at the immature B cell stage is sufficient to promote editing.