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Publication : Age-Associated B Cells Express a Diverse Repertoire of V<sub>H</sub> and Vκ Genes with Somatic Hypermutation.

First Author  Russell Knode LM Year  2017
Journal  J Immunol Volume  198
Issue  5 Pages  1921-1927
PubMed ID  28093524 Mgi Jnum  J:252217
Mgi Id  MGI:5925868 Doi  10.4049/jimmunol.1601106
Citation  Russell Knode LM, et al. (2017) Age-Associated B Cells Express a Diverse Repertoire of VH and Vkappa Genes with Somatic Hypermutation. J Immunol 198(5):1921-1927
abstractText  The origin and nature of age-associated B cells (ABCs) in mice are poorly understood. In this article, we show that their emergence required MHC class II and CD40/CD40L interactions. Young donor B cells were adoptively transferred into congenic recipients and allowed to remain for 1 mo in the absence of external Ag. B cells expressing the T-bet transcription factor, a marker for ABCs, were generated after multiple cell divisions from C57BL/6 donors but not from MHC class II- or CD40-deficient donors. Furthermore, old CD154 (CD40L)-deficient mice did not accrue ABCs, confirming that they arise primarily through T-dependent interactions. To determine what Igs ABCs express, we sequenced VH and Vkappa rearranged genes from unimmunized 22-mo-old C57BL/6 mice and showed that they had a heterogeneous repertoire, which was comparable to that seen in old follicular and marginal zone B cell subsets. However, in contrast to the follicular and marginal zone cells, ABCs displayed significant somatic hypermutation. The mutation frequency was lower than found in germinal center cells after deliberate immunization, suggesting that ABCs have undergone mild stimulation from endogenous Ags over time. These observations show that quiescent ABCs are Ag-experienced cells that accumulate during T cell-dependent responses to diverse Ags during the life of an individual.
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