Germinal center (GC) B cells cycle between the dark zone (DZ) and light zone (LZ) during antibody affinity maturation. Whether this movement is necessary for GC function has not been tested. Here we show that CXCR4-deficient GC B cells, which are restricted to the LZ, are gradually outcompeted by WT cells indicating an essential role for DZ access. Remarkably, the transition between DZ centroblast and LZ centrocyte phenotypes occurred independently of positioning. However, CXCR4-deficient cells carried fewer mutations and were overrepresented in the CD73(+) memory compartment. These findings are consistent with a model where GC B cells change from DZ to LZ phenotype according to a timed cellular program but suggest that spatial separation of DZ cells facilitates more effective rounds of mutation and selection. Finally, we identify a network of DZ CXCL12-expressing reticular cells that likely support DZ functions.
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http://dx.doi.org/10.1016/j.immuni.2013.08.038 | DOI Listing |
Vaccines (Basel)
January 2025
Smorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia.
Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.
View Article and Find Full Text PDFNat Commun
January 2025
Dept. of Microbiology and Immunology, Center for Microbial Pathogenesis and Host Inflammatory Responses, and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined.
View Article and Find Full Text PDFCell Death Differ
January 2025
Laboratory for Experimental Leukemia and Lymphoma Research (ELLF), LMU University Hospital, Munich, Germany.
The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.
View Article and Find Full Text PDFPathol Res Pract
January 2025
Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands; Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom. Electronic address:
Background: Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host's anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305.
Immunological interventions, like vaccinations, are enabled by the predictive control of humoral responses to novel antigens. While the development trajectories for many broadly neutralizing antibodies (bnAbs) have been measured, it is less established how human subtype-specific antibodies develop from their precursors. In this work, we evaluated the retrospective development trajectories for eight anti-SARS-CoV-2 Spike human antibodies (Abs).
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