Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection.

Immunity

Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.

Published: November 2013

AI Article Synopsis

  • Germinal center B cells migrate between the dark zone (DZ) and light zone (LZ) for antibody affinity maturation, and research shows that this movement is crucial for their function.
  • CXCR4-deficient B cells, which are stuck in the LZ, are outcompeted by wild-type (WT) cells, suggesting that access to the DZ is important for effective mutation and selection.
  • The study also reveals that a network of CXCL12-expressing reticular cells in the DZ may support these essential functions, highlighting the importance of spatial arrangement in immune responses.

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828484PMC
http://dx.doi.org/10.1016/j.immuni.2013.08.038DOI Listing

Publication Analysis

Top Keywords

germinal center
8
phenotype timed
8
dark zone
8
cxcr4-deficient cells
8
cells
7
center centroblasts
4
centroblasts transition
4
transition centrocyte
4
centrocyte phenotype
4
timed program
4

Similar Publications

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 PDF

Intrinsic p53 activation restricts gammaherpesvirus driven germinal center B cell expansion during latency establishment.

Nat 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 PDF

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 PDF

Intra-patient comparison of microarchitecture of tumour negative lymph nodes from oesophageal cancer patients - Results from the MRC Oe02 trial.

Pathol 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 PDF

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).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!