title: L chain allelic inclusion does not increase autoreactivity in lupus-prone New Zealand Black/New Zealand White mice.
abstract: L chain allelic inclusion has been proposed as a B cell tolerance mechanism in addition to clonal deletion, clonal anergy, and receptor editing. It is said to rescue autoreactive B cells from elimination by diluting out the self-reactive BCR through the expression of a second innocuous L chain. In autoimmune animals, such as lupus-prone mice, allelically included B cells could be activated and produce pathogenic autoantibodies. We have previously shown that anti-DNA hybridomas from diseased New Zealand Black/New Zealand White F1 mice exhibit nearly perfect allelic exclusion. In the current study, we have analyzed single B cells from these and from nonautoimmune mice. In addition, we have cloned and expressed the Ig variable regions of several L chain-included B cells in cell culture. We find that although the number of L chain-included B cells increases as a result of receptor editing, the majority of such cells do not retain an autoreactive HxL chain combination and, therefore, allelic inclusion in itself does not serve as a B cell tolerance mechanism in these autoimmune mice.
authors: Department of Medicine, Hadassah University Hospital, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.
authors: Efi
authors: E
authors: Makdasi
authors: Dan
authors: D
authors: Eilat
mesh_terms: D000483:Alleles; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D005260:Female; D055879:Gene Knock-In Techniques; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D017634:Self Tolerance / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007147:Immunoglobulin Light Chains