Although it is well established that pre-BCR signaling governs proliferation and differentiation during B cell development, the components of the pre-BCR that are important for signaling are a matter of controversy. It has been suggested that signaling by the μ heavy chains of the pre-BCR induces survival and differentiation of pre-B cells, while the λ5 part of the pre-BCR is essential for proliferation and clonal expansion. However, the mechanism by which pre-BCR μ chains initiate differentiation signals is not clear. Using two variants of a murine B-lymphocyte cell line that differ only in surface expression of either BCR or pre-BCR, we demonstrated that surface μ chains in the pre-BCR are of the high-mannose type only, while those in the BCR are of the complex type. It is hypothesized that mannose-specific lectin-like molecules on accessory cells or in solution may function as the non-antigen ligand that triggers the pre-BCR.
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http://dx.doi.org/10.1016/j.molimm.2010.07.005 | DOI Listing |
Mol Immunol
February 2024
Department of Immunology, National Institute of Infectious Diseases, Shinjuku, Tokyo 162-8640, Japan.
During B cell development, pre-B cell receptor (pre-BCR), comprising the immunoglobulin heavy chain (HC) and surrogate light chain (SLC), plays a crucial role. The expression of pre-BCR serves as a certification of HC quality, confirming its ability to associate with the SLC and light chain (LC). In mice lacking SLC, the absence of this quality control mechanism leads to a distorted repertoire of HCs in the spleen and bone marrow.
View Article and Find Full Text PDFElife
January 2024
Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
The ratio between κ and λ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells.
View Article and Find Full Text PDFJ Immunol
July 2023
Department of Microbiology and Immunology, Western Infection, Immunity and Inflammation Centre, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada; and Division of Genetics and Development, Children's Health Research Institute, Lawson Research Institute, London, ON, Canada.
B cell development requires the ordered rearrangement of Ig genes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags. Igκ rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26 transformation-specific transcription factor Spi-C is activated in response to dsDNA double-stranded breaks in small pre-B cells to negatively regulate pre-BCR signaling and Igκ rearrangement.
View Article and Find Full Text PDFSci Immunol
June 2022
Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
The SKIV2L RNA exosome is an evolutionarily conserved RNA degradation complex in the eukaryotes. Mutations in the gene are associated with a severe inherited disorder, trichohepatoenteric syndrome (THES), with multisystem involvement but unknown disease mechanism. Here, we reported a THES patient with mutations showing severe primary B cell immunodeficiency, hypogammaglobulinemia, and kappa-restricted plasma cell dyscrasia but normal T cell and NK cell function.
View Article and Find Full Text PDFDuring bone marrow B-cell development, the pre-B-cell receptor is formed by the association of the immunoglobulin heavy chain with a surrogate light chain, which is encoded by the VPREB1, and λ5 genes. It is known that pre-BCR signaling signifies a critical checkpoint at the pre-B-cell stage. Thus, failure pre-BCR signaling is proposed as a critical factor for the development of B-cell acute lymphoblastic leukemia (B-ALL).
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