International Immunology Advance Access originally published online on October 4, 2005
International Immunology 2005 17(11):1447-1461; doi:10.1093/intimm/dxh323
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An antibody VH gene that promotes marginal zone B cell development and heavy chain allelic inclusion
Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
1 Present address: Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
Correspondence to: T. Manser; E-mail: manser{at}mail.jci.tju.edu
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 Ig
and Igß, 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 VH ‘knockin’ mice in which the transgene-encoded VH region differs by eight amino acid residues from the VH region in a VH 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.
Keywords: antibody heavy chain, B cell, development, transgenic mice
* These authors contributed equally to this work.
Transmitting editor: J. Ravetch
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