role of Igalpha and Igbeta during avian B cell development.
Published: 2005
Language: eng
Number of pages: 217
Description: Surface immunoglobulin (sIg) expression has been conserved as a critical checkpoint during B cell development, although it has remained controversial whether ligation of the B cell receptor (BCR) complex is required. Work presented in this thesis has addressed this controversy by fusing the extracellular and transmembrane domains of murine CD8alpha and CD8beta (mCD8alpha, mCD8beta) to the cytoplasmic domains of chicken Igalpha and Igbeta (chIgalpha, chIgbeta), thereby targeting Igalpha and Igbeta to the plasma membrane in the absence of any of the extracellular domains associated with the BCR complex. Retroviral gene transfer was used to introduce these chimeric proteins into B cell precursors in developing chick embryos. Surface expression of either the mCD8alpha:chIgalpha + mCD8beta:chIgbeta chimeric heterodimer, or the mCD8alpha:chIgalpha chimeric homodimer alone, supported bursal colonization, B cell proliferation and gene conversion. Thus ligand-independent signaling following surface expression of either the Igalpha/beta heterodimer, or the Igalpha homodimer, is sufficient to support the early stages of avian B cell development. Site directed mutagenesis demonstrated that the Igalpha ITAM tyrosines, as well as an additional tyrosine provided by either the conserved Igalpha non-ITAM tyrosine or the Igbeta ITAM tyrosines, are required during B cell development. Strikingly B cell differentiation was selectively inhibited by the expression of a mCD8alpha:chIgbeta chimeric homodimer, formally proving that avian Igalpha and Igbeta are not functionally redundant during avian B cell development. Due to the presence of non-infected developing B cells within infected chick embryos, this work represents the first evidence that ligand-independent signaling is as efficient as the endogenous Ig receptor complex in supporting B cell development.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5312.

Thesis (Ph.D.)--University of Toronto, 2005.

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