Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Collaborative Specialization

Developmental Biology

Supervisor

DeKoter, Rodney P.

Abstract

The activation of B cells culminates in a fate decision between plasma cell or memory B cell differentiation pathways. Mice lacking the Ets transcription factor Spi-B exhibit impaired secondary antibody (Ab)-forming responses. The role of the related factor Spi-C in Ab-forming responses remains unknown. Using Spib-/-Spic+/- mice, we showed that heterozygosity of Spi-C rescued reductions in secondary IgG1-secreting cell frequencies. Spib-/- and Spib-/-Spic+/- B cells generated increased frequencies of CD138+ cells, relative to WT B cells. Spib-/- B cells underwent accelerated differentiation compared to WT B cells, while Spib-/-Spic+/- B cells exhibited a lag in differentiation. Gene expression analysis indicated that Bach2 was downregulated in CD138+ Spib-/- cells. ChIP experiments suggested that Spi-B and Spi-C were enriched at Ets binding sites located within Bach2 in stimulated B cells. Our results point to a novel role for Spi-C in opposing the function of Spi-B in activated B cells.

Included in

Immunity Commons

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