Pre-B cell receptor-mediated selection of pre-B cells synthesizing functional mu heavy chains.
Ig gene rearrangements could generate V(H)-D-J(H) joining sequences that interfere with the correct folding of a mu-chain, and thus, its capability to pair with IgL chains. Surrogate light (SL) chain might be the ideal molecule to test the capacity of a mu-chain to pair with a L chain early in development, in that only pre-B cells that assemble a membrane mu-SL complex would be permitted to expand and further differentiate. We have previously identified two SL chain nonpairing V(H)81X-mu-chains with distinct V(H)-D-J(H) joining regions. Here, we show that one of these V(H)81X-mu-chains does not rescue B cell development in J(H) knock-out mice, because flow cytometric analysis of bone marrow cells from V(H)81X-mu transgenic J(H) knock-out mice revealed normal numbers of pro-B cells, but essentially no pre-B and surface IgM+ B cells. Immunoprecipitation analysis of transfected pre-B and hybridoma lines revealed that the same mu-chain fails to pair not only with SL chain but also with four distinct kappa L chains. These findings demonstrate that early pre-B cells are selected for maturation on the basis of the structure of a mu-chain, in particular its V(H)-D-J(H) joining or CDR3 sequence, and that one mechanism for this selection is the capacity of a mu-chain to assemble with SL chain. Therefore, we propose a new function of SL chain in early B cell development: SL chain is part of a quality control mechanism that tests a mu-chain for its ability to pair with conventional L chains.
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
G H
GH
Kline
L
L
Hartwell
G B
GB
Beck-Engeser
U
U
Keyna
S
S
Zaharevitz
N R
NR
Klinman
H M
HM
Jäck
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*
D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell