A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly.
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 mu 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 mu 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.
Wasserman
R
R
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Li
Y S
YS
Shinton
S A
SA
Carmack
C E
CE
Manser
T
T
Wiest
D L
DL
Hayakawa
K
K
Hardy
R R
RR
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell