The human heavy chain Ig V region gene repertoire is biased at all stages of B cell ontogeny, including early pre-B cells.

  • Kraj P
  • Rao S
  • Glas A
  • et al.
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Abstract

The expressed human Ig repertoire is not an equal representation of all V(H) segments present in genomic DNA. Studies have shown that a restricted set of V(H) gene segments are over-represented in Ab repertoires of fetal/neonatal and adult B cells. Additionally, this restricted set of V(H) genes is frequently expressed by autoimmune and tumor B cells. To investigate at which developmental stage a bias in the repertoire begins, we compared the V(H)3 and V(H)4 family repertoires of pre-B and immature B cells from bone marrow and mature B cells from peripheral blood of two adults. We found that the V4-34 and V4-59 gene segments of the V(H)4 family and the V3-23 gene segment of the V(H)3 family dominate the repertoires of the surface Ig-negative early pre-B as well as immature and mature B cells. Furthermore, the pattern of utilization of other V(H)3 family members suggests that certain genes that are frequently rearranged during early stages of B cell development are subsequently disfavored during later stages of B cell maturation. We conclude that the over-representation of certain V genes could arise from sequential mechanisms operating at both early and later stages of B cell development. These V(H)-mediated mechanisms might include preferential rearrangement and/or efficiency of pairing with the surrogate light chain at the surface Ig-negative, early pre-B cell stage and ligand selection at more mature, surface Ig-positive, B cell stages.

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Kraj, P., Rao, S. P., Glas, A. M., Hardy, R. R., Milner, E. C., & Silberstein, L. E. (1997). The human heavy chain Ig V region gene repertoire is biased at all stages of B cell ontogeny, including early pre-B cells. The Journal of Immunology, 158(12), 5824–5832. https://doi.org/10.4049/jimmunol.158.12.5824

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