Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 1, Pages 452-461Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0804060
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Funding
- National Institutes of Health [U01 DK070430, AR34156, RO1 DE017590]
- Alliance for Lupus Research
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007775] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR034156] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE017590] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK070430] Funding Source: NIH RePORTER
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Studies in autoantibody transgenic mice have demonstrated receptor editing rearrangements at Ab H and L chain loci. However, the physiologic role of H chain editing (V-H replacement and rearrangement on the second allele) has been called into question. It is unclear if additional rounds of H chain rearrangement are driven by BCR specificity. In this study, we analyze the manner in which B cells undergo additional H chain rearrangements in an anti-DNA H chain knock-in mouse, B6.56R. We find that rearrangements in 56R(+) B cells tend to involve the D gene locus on both alleles and the most J(H)-proximal V-H gene segments on the endogenous allele. As a result, some B cells exhibit V(D)J rearrangements on both H chain alleles, yet allelic exclusion is tightly maintained in mature 56R B cells. As B cells mature, a higher proportion expresses the nontransgenic H chain allele. Rearrangements on both H chain alleles exhibit junctional diversity consistent with TdT-inediated N-addition, and TdT RNA is expressed exclusively at the pro-B cell stage in B6.56R. Collectively, these findings favor a single, early window of H chain rearrangement in B6.56R that precedes the expression of a functional BCR. B cells that happen to successfully rearrange another H chain may be favored in the periphery. The Journal of Immunology, 2009, 183: 452-461.
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