Autoreactive anti-DNA transgenic B cells in lupus-prone New Zealand black/New Zealand white mice show near perfect L chain allelic exclusion.
Recent work on B cell tolerance and autoimmunity has suggested the L chain allelic inclusion is a property of autoreactive B cells and is closely linked to receptor editing. Allelic inclusion could rescue autoreactive B cells from clonal deletion by reducing their effective BCR surface density. We have investigated this phenomenon in anti-DNA producing hybridomas, derived from different strains of Ig gene-targeted, lupus-prone NZB/NZW mice. Our results indicate that isotype and allelic exclusion was strictly maintained in most high- and low-affinity, edited and nonedited, anti-DNA transgenic B cells. However, a substantial fraction of the anti-DNA hybridomas expressed a very restricted set of nonproductively rearranged L chain mRNA, in addition to the productive anti-DNA L chain. The aberrant L chains could have a role in the selection and survival of autoreactive B cells in these autoimmune mice.
Makdasi
Efi
E
Department of Medicine, Hadassah University Hospital, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Fischel
Ruth
R
Kat
Inbal
I
Eilat
Dan
D
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017637:Clonal Deletion; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell