The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/1/259/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 2, January 19, 1998 259-264

Brief Definitive Reports

A Novel Mechanism for B Cell Repertoire Maturation Based on Response by B Cell Precursors to Pre–B Receptor Assembly

R. Wasserman*, Y.-S. Li*, S.A. Shinton*, C.E. Carmack*, T. Manser{ddagger}, D.L. Wiest*, K. Hayakawa*, and R.R. Hardy*

From the * Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and the {ddagger} Kimmel Cancer Institute, Thomas Jefferson Medical College, Philadelphia, Pennsylvania 19107

The expression of different sets of immunoglobulin specificities by fetal and adult B lymphocytes is a long-standing puzzle in immunology. Recently it has become clear that production of immunoglobulin µ heavy chain and subsequent assembly with a surrogate light chain to form the pre-B cell receptor complex is critical for development of B cells. Here we show that instead of promoting pre–B cell progression as in adult bone marrow, this complex inhibits pre–B cell growth in fetal liver. Curiously, we identify a fetal-associated VH11 µ heavy chain that allows continued pre-B proliferation in fetal liver. Interestingly, this heavy chain does not associate efficiently with a surrogate light chain, providing a previously unrecognized mechanism for skewing the expression of distinctive VH genes toward fetal through early neonatal life.

Address correspondence to Dr. Richard R. Hardy, Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: 215-728-2463; Fax: 215-728-2412; E-mail rr_hardy{at}fccc.edu

R. Wasserman's current address is Division of Oncology, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. Y.-S. Li's current address is Beijing Sai-Yin-Si Institute of Biotechnology, Beijing 100024, China. C.E. Carmack's present address is Molecular Dynamics, 928 East Arques Ave., Sunnyvale, CA 94086-4520.


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