title: Direct reduction of antigen receptor expression in polyclonal B cell populations developing in vivo results in light chain receptor editing.
abstract: 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.
authors: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors: Shixue
authors: S
authors: Shen
authors: Tim
authors: T
authors: Manser
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D017393:RNA Editing / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell