B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development

doi:10.1084/jem.190.4.471

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J. Exp. Med., Volume 190, Number 4, August 16, 1999 471-478
Copyright © 1999 by The Rockefeller University Press.

B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development

Kong-Peng Lam^a and Klaus Rajewsky^b
^a From the Institute of Molecular and Cell Biology, The National University of Singapore, Singapore 117609, Republic of Singapore
^b Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany

Correspondence to: Kong-Peng Lam, Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Drive, Singapore 117609, Republic of Singapore. Tel:65-874-3784 Fax:65-779-1117 E-mail:mcblamkp{at}imcb.nus.edu.sg.

Mice expressing the immunoglobulin (Ig) heavy (H) chain variable(V) region from a rearranged V_H12 gene inserted into the IgHlocus generate predominantly B-1 cells, whereas expression oftwo other V_H region transgenes (V_HB1-8 and V_HglD42) leads tothe almost exclusive generation of conventional, or B-2, cells.To determine the developmental potential of B cells bearingtwo distinct B cell antigen receptors (BCRs), one favoring B-1and the other favoring B-2 cell development, we crossed V_H12insertion mice with mice bearing either V_HB1-8 or V_HglD42. Bcells coexpressing V_H12 and one of the other V_H genes are readilydetected in the double IgH insertion mice, and are of the B-2phenotype. In mice coexpressing V_H12, V_HB1-8 and a transgenic ${kappa}$ chain able to pair with both H chains, double H chain–expressingB-2 cells, and B-1 cells that have lost V_HB1-8 are generated,whereas V_HB1-8 single producers are undetectable. These datasuggest that B-1 but not B-2 cells are selected by antigenicstimuli in whose delivery BCR specificity and surface densityare of critical importance.

Key Words: B-1 cells, B-2 cells, immunoglobulin heavy chain, allelic inclusion,gene targeting

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