International Immunology, Vol. 12, No. 6, 873-885,
June 2000
© 2000 Japanese Society for Immunology
Positive and negative selection of antigen-specific B cells in transgenic mice expressing variant forms of the VH1 (T15) heavy chain
National Institutes of Health, National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
1 Intramural Research Support Program/SAIC–Frederick, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
2 Institute for Cellular and Molecular Biology, University of Texas at Austin, ESB-534, Austin, TX 78712, USA
3 Department of Microbiology and Immunology, University of Michigan Medical School, Building II, M6740 Medical Sciences, Ann Arbor, MI 48109, USA
Correspondence to: J. J. Kenny
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 VH1+ 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 µMT knockout mouse in which surface expression of endogenous H chains is blocked, the percent of splenic VH1+ 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.
Keywords: antigen binding, B lymphocytes, generation of diversity, H chain transgenic mice, idiotype, positive selection, phosphocholine
Transmitting editor: J. J. Kenny
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