Association of the pre-B cell receptor (BCR) expression level with the quality of pre-BII cell differentiation reveals hierarchical pre-BCR function.
The expression of a pre-B cell receptor (pre-BCR) is required for allelic exclusion and pre-BII cell differentiation. V(H)12 microH chains are unusual in that they form pre-BCRs and mediate allelic exclusion, but most cannot drive pre-BII cell differentiation. To explain this paradox, we examined pre-BCR functions and pre-BII cell differentiation in mice expressing microH chain transgenes encoding a B cell-permissible V(H)12 microH chain (designated 10/G4(6-1)), and a non-permissible V(H)12 microH chain (designated 8/G0). Compared with 10/G4 pre-BCRs, 8/G0 pre-BCRs are expressed at low levels on the cell surface. 8/G0 pre-BCRs mediate allelic exclusion, but 8/G0 pre-BII cells are defective in proliferation and expression of survival factors Bcl-2, Bcl-X(L) and hemokinin 1 (HK1). Increasing 8/G0 microH chain production restores HK1 transcription and improves proliferation of pre-BII cells as well as later stage B cell development. These data reveal a hierarchy of pre-BCR function that determines the development and plasticity of early B cells.
Wang
Hongsheng
H
Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852, USA.
Clarke
Stephen H
SH
D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry; D006720:Homozygote; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D015320:Tachykinins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism
C494812:Bcl2l1 protein, mouse; D015851:Interleukin-7; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011498:Protein Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; C423233:Tac4 protein, mouse; D015320:Tachykinins; D051020:bcl-X Protein