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Publication : An antibody VH gene that promotes marginal zone B cell development and heavy chain allelic inclusion.

First Author  Heltemes-Harris L Year  2005
Journal  Int Immunol Volume  17
Issue  11 Pages  1447-61
PubMed ID  16204304 Mgi Jnum  J:102308
Mgi Id  MGI:3607350 Doi  10.1093/intimm/dxh323
Citation  Heltemes-Harris L, et al. (2005) An antibody VH gene that promotes marginal zone B cell development and heavy chain allelic inclusion. Int Immunol 17(11):1447-61
abstractText  The Ig heavy (H) chain plays a pivotal role in the regulation of primary B cell development through its association with a variety of other proteins including Igalpha and Igbeta, the surrogate light chain components and bona fide L chains, to form transmembrane signaling complexes. Little is known about how alterations in the structure of the H chain variable region influence association with these proteins, or the signaling capacity of the complexes that form. Here we describe a line of V(H) 'knockin' mice in which the transgene-encoded V(H) region differs by eight amino acid residues from the V(H) region in a V(H) knockin line we previously constructed and characterized. The transgenic H chain locus in the line of mice we characterized earlier efficiently promotes H chain allelic exclusion and all phases of primary B cell development, resulting in the generation of mature B1, marginal zone (MZ) and follicular (FO) B cell compartments. In contrast, the transgenic H chain locus in the new line fails to enforce allelic exclusion, as evidenced by the majority of peripheral B cells expressing two H chains on their surfaces. Moreover, this locus inefficiently drives bone marrow B lymphopoiesis and FO B cell development. However, this H chain locus does promote MZ B cell development, from precursors that appear to be generated during fetal and neonatal life. We discuss these data in the context of previous findings on the influence of Ig H chain structure on primary B cell development.
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