Biased V(H) gene usage in early lineage human B cells: Evidence for preferential Ig gene rearrangement in the absence of selection

Sambasiva P. Rao, Jeffrey M. Riggs, David F. Friedman, Michael S. Scully, Tucker W. LeBien, Leslie E. Silberstein

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Certain V(H) genes are predominantly expressed in mature B cells. We hypothesized that several, mutually nonexclusive V(H)-dependent mechanisms operating at distinct stages during B cell development may be responsible for overrepresentation of these V(H) genes. In the present study, we have assessed whether one of the mechanisms involves preferential rearrangement at the pro-B cell stage. The frequency of individual V(H)4 and V(H)3 genes in rearrangement libraries from FACS-purified human CD34+/CD19+ pro-B and CD34-/CD19+ pre-B cells was assessed. The in-frame and out-of-frame rearrangements from both cell populations were analyzed using a high resolution PAGE system. The frequencies of individual V(H) gene segments among out-of-frame rearrangements from pro-B cells were determined, because these frequencies should reflect only processes before the translation of the μ-heavy chain and should not be biased by selection mechanisms. Our results demonstrate that, at the pro-B cell stage, the V4-34, V4-39, and V4-59 gene segments are the most frequently rearranged V(H)4 family genes, and the V3-23 and V3-30 gene segments are the most frequently rearranged V(H)3 family genes. This finding suggests that the predominant expression of these V(H) genes in peripheral mature B cells is determined to a significant degree by their preferential rearrangement during V-DJ recombination.

Original languageEnglish (US)
Pages (from-to)2732-2740
Number of pages9
JournalJournal of Immunology
Volume163
Issue number5
StatePublished - Sep 1 1999

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