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

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Abstract
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.