Negative selection at the pre-BCR checkpoint elicited by human mu heavy chains with unusual CDR3 regions.
Approximately 9% of in-frame mu heavy chain transcripts found in normal human pro-B cells encode proteins that can be expressed on the cell surface in the absence of surrogate or conventional light chains. These unusual mu heavy chains demonstrate preferential use of certain VH genes (VH3-23), frequent expression of DH regions in underrepresented reading frames, and an increased number of positively charged amino acids within the CDR3 region. Transcripts for these proteins are not found in pre-B cells or in mature B cells. When expressed in Jurkat T cells with the Ig(alpha)/Ig(beta) signal transduction module, these aberrant mu heavy chains induce cell activation and apoptosis. These results suggest that some mu heavy chains elicit negative selection at the pro-B cell to pre-B cell transition.
Minegishi
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Department of Immunology, St. Jude Children's Research Hospital, University of Tennessee College of Medicine, Memphis, TN 38105, USA.
Conley
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ME
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019556:COS Cells; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000276:immunology; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction
D022801:Complementarity Determining Regions; D007147:Immunoglobulin Light Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell