title: Positive and negative selection of antigen-specific B cells in transgenic mice expressing variant forms of the V(H)1 (T15) heavy chain.
abstract: Four variant forms of the V1 (T15-H chain) gene are synthesized in mice. Each V1 variant pairs with a distinct L chain to produce a binding site having specificity for phosphocholine (PC). Transgenic mice expressing variant forms of the V1 gene were analyzed to elucidate the factors driving B cell selection into the peripheral repertoire. In all four lines of H chain transgenic mice analyzed, transgene expression caused complete allelic exclusion of endogenous H chains in the bone marrow (BM), whereas most splenic B cells expressed endogenous H chains. The number of sIgM(+) BM B cells and their sIg receptor number was reduced compared to that of normal transgene-negative controls, suggesting that B cells expressing transgene-encoded H chains were being negatively selected in the BM. Mice expressing autoreactive forms of the V1 transgene with lower affinity for PC (M603H and M167H) exhibit positive selection of PC-specific B cells into the spleen, whereas mice expressing the higher affinity T15H variant exhibited elevated PC-specific B cells in the peritoneal cavity but few V(H)1(+) splenic B cells. These data suggest that the higher affinity T15-id(+) B cells preferentially survive in the peritoneal cavity. When these H chain transgenes were crossed into the mu MT knockout mouse in which surface expression of endogenous H chains is blocked, the percent of splenic V(H)1(+) PC-specific B cells increased up to 5-fold and T15-id(+) B cells were detectable in the spleen of T15H mice. This implies that T15-id(+) PC-specific B cells can be selected into the periphery, but they compete poorly with follicular B cells expressing endogenous Ig.
authors.affiliation: National Institutes of Health, National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kenny
authors.forename: E G
authors.initials: EG
authors.lastname: Derby
authors.forename: J A
authors.initials: JA
authors.lastname: Yoder
authors.forename: S A
authors.initials: SA
authors.lastname: Hill
authors.forename: R T
authors.initials: RT
authors.lastname: Fischer
authors.forename: P W
authors.initials: PW
authors.lastname: Tucker
authors.forename: J L
authors.initials: JL
authors.lastname: Claflin
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010767:Phosphorylcholine / Q000276:immunology*
chemical_list: D018956:CD5 Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin