Germinal Center Dynamics Revealed by Multiphoton Microscopy Using a Photoactivatable Fluorescent Reporter
By Gabriel D. Victora, T. Schwickert, David R. Fooksman, A. Kamphorst, M. Meyer-Hermann, Michael Loran Dustin, Michel C. Nussenzweig. Cell, 2010
1,189 citations recorded by the source corpus.
SUMMARY The germinal center (GC) reaction produces high-affinity antibodies by random mutation and selective clonal expansion of B cells with high-affinity receptors. However, the mechanism by which B cells are selected remains unclear, as does the role of the two anatomically-defined areas of the GC, light zone (LZ) and dark zone (DZ). We combined a new transgenic photoactivatable green fluorescent protein (PA-GFP) tracer with multiphoton laser-scanning microscopy and flow cytometry to examine anatomically defined LZ and DZ B cells and GC selection. We find that B cell division is restricted to the DZ, and that there is a net vector of B cell movement from the DZ to the LZ. The decision to return from the LZ to the DZ and undergo clonal expansion is controlled by T cells, which discern between LZ B cells based on the amount of antigen captured, providing a mechanism for GC selection.
Subfields: Biophysics, Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/93207b24d515af79a364095e875919d440f36d74
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Citations in the corpus
- T follicular helper cell differentiation, function, and roles in disease (2014, background): “Indiscriminate Tfh cell help to both high and low affinity B cells leads to the generation of lower affinity antibodies over time (Victora et al., 2010).”
- Immunological Principles Guiding the Rational Design of Particles for Vaccine Delivery. (2017, neutral): “antigens by sequential rounds of proliferation and competition for limited CD40Ldependent help from T follicular helper (Tfh) cells.(56) B cells exiting germinal centers can”
- Follicular Helper T Cells. (2016, background): “B cells that have higher affinity BCRs as a consequence of SHM are more likely to pick up antigen from FDCs and, after processing this, elicit limiting T cell help (32).”
- Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses (2013, neutral): “Given that Tfh cells can be a limiting factor for B cell responses (Johnston et al., 2009; Victora et al., 2010) and that Tfh cells are associated with better antibody responses to simian immunodeficiency virus (Petrovas et al.”
- GERMINAL CENTER B CELL DYNAMICS (2016, neutral): “…to re-enter the DZ for further rounds of proliferation and SHM. Recent studies have provided ample experimental evidence for the re-entry of selected B cells from LZ to DZ upon antigen-driven selection (Allen et al., 2007b; Gitlin et al., 2014; Schwickert et al., 2007; Victora et al., 2010).”