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Analysis of the Molecular and Functional Role of the Adaptor Protein HSH2. Studies are ongoing to elucidate the functional role that the adaptor protein HSH2 plays in regulating B cell biology. HSH2 is selectively expressed in cells of the B lineage and its expression is up-regulated in vitro in response to agonists that promote B cell survival and differentiation, including CD40L, BLyS, LPS and CpG DNA. Recent studies using transgenic mice have revealed that HSH2 plays a critical role in regulating terminal differentiation of B cells into antibody secreting plasma cells. Constitutive expression of HSH2 in the B lineage results in a significant decrease in serum immunoglobulin (Ig) titers. Moreover, immunization of HSH2 Tg mice with either T-dependent or T-independent antigens induces only a modest antigen-specific IgM response and very little class-switched Ig production. Conversely immunization of mice in which HSH2 is expressed at only one fifth the normal amount in B cells (HSH2 hypomorph mice), leads to enhanced production of antigen-specific class switched Ig both in terms of the kinetics and magnitude of the response when compared to wild type mice. Based on these observations, it is likely that HSH2 plays a critical role in regulating Ig class switching and terminal differentiation of B cells. Future studies will be conducted to:
Identify important regions/motifs of HSH2 that are involved in its function
Identify the proteins that interact with HSH2 in B lymphocytes and assess their functional importance
Characterize the molecular mechanisms that control HSH2 expression in B cells
Generate conditional knockout mice to examine the importance of HSH2 in regulation of B cell development, activation and differentiation
Identify important regions/motifs of HSH2 that are involved in its function
Identify the proteins that interact with HSH2 in B lymphocytes and assess their functional importance
Characterize the molecular mechanisms that control HSH2 expression in B cells
Generate conditional knockout mice to examine the importance of HSH2 in regulation of B cell development, activation and differentiation
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Journal of Immunologyno. 1 (2023): 231.08-231.08
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