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- W4313373096 abstract "Abstract The existence of diverse B cell antigen receptor (BCR) specificities is essential for development of protective antibody responses against a wide variety of pathogens. In developing B cells, the BCR repertoire is crafted through sequential rearrangements of heavy and light chain genes, and involves both combinatorial and junctional diversification catalyzed by recombinases and nucleases. Mature B cells undergo further diversification in peripheral lymphoid organs through isotype switching and somatic hypermutations in response to foreign antigens; although these events are not known to alter BCR antigen specificity. Cytoskeletal proteins modulate BCR signal strength and thereby antibody responses, but it is not known if they play a role in the generation of BCR diversity. Using next generation sequencing, and iRepertoire, Inc and ImMunoGeneTics (IMGT) software platforms we examined BCR repertoires in developing and mature B cells that lack the expression of Ezrin, a prominent cytoskeletal regulator of BCR organization, signaling and activation. We show that Ezrin deficiency impacts the generation of BCR repertoire diversity during B cell development, as well as the mature BCR repertoire. Our analysis provides a window into the major processes involved in diversifying the B cell repertoire in control and Ezrin-deficient B cells, including V gene usage, number, frequency and length of unique CDR3s, nucleotide additions and trimming, and shared and unique clonotypes. Our data suggest that the Ezrin cytoskeleton in B cells impacts humoral immunity not only through modulation of B cell activation upon foreign antigen encounter, but also through qualitative and quantitative modulation of the available BCR repertoire." @default.
- W4313373096 created "2023-01-06" @default.
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- W4313373096 date "2020-05-01" @default.
- W4313373096 modified "2023-09-26" @default.
- W4313373096 title "Cytoskeletal control of the developing and mature B cell antigen receptor repertoire" @default.
- W4313373096 doi "https://doi.org/10.4049/jimmunol.204.supp.151.13" @default.
- W4313373096 hasPublicationYear "2020" @default.
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