Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / chemistry
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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Bone Marrow / immunology
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Cell Differentiation
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Cell Membrane / chemistry
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Homozygote
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Interleukin-7 / pharmacology
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Lymphocyte Activation* / genetics
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Membrane Glycoproteins / analysis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Transgenic
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Pre-B Cell Receptors
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Protein Precursors / analysis
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Protein Precursors / genetics
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Protein Precursors / metabolism
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Proto-Oncogene Proteins c-bcl-2 / analysis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Receptors, Antigen, B-Cell / analysis
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / metabolism*
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Spleen / immunology
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Tachykinins / analysis
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Tachykinins / genetics
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Tachykinins / metabolism
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bcl-X Protein / analysis
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bcl-X Protein / genetics
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bcl-X Protein / metabolism
Substances
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Bcl2l1 protein, mouse
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Interleukin-7
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Membrane Glycoproteins
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Pre-B Cell Receptors
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Protein Precursors
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Receptors, Antigen, B-Cell
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Tac4 protein, mouse
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Tachykinins
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bcl-X Protein