Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter

Victora, Gabriel D.; Schwickert, Tanja A.; Fooksman, David R.; Kamphorst, Alice O.; Meyer‐Hermann, Michael; Dustin, Michael L.; Nussenzweig, Michel C.

doi:10.1016/j.cell.2010.10.032

Cited by 1,000 publications

(1,457 citation statements)

References 74 publications

(125 reference statements)

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“…This is particularly important for affinity-dependent extraction of the antigen, where the bonds need to sustain extraction forces before the antigen is separated from the APC and endocytosed by the B cell 80 . Since the amount of antigen extracted by B cells and presented to T cells is the primary determinant of affinity-based B cell clonal selection 145,146 , mechanical extraction of antigen provides an advantage for high-affinity B cells during antibody responses 144 .…”

Section: [H1] Cytoskeletal Regulation Of Biomechanicsmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

118

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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Section: [H1] Cytoskeletal Regulation Of Biomechanicsmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

118

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“…B cells then exit into the light zones, where those cells expressing surface Ig of sufficiently high affinity to enable them to efficiently acquire antigen from FDCs undergo further interactions with Tfh cells and receive signals, in particular via CD40, that enable continued survival. Tfh cells thus, select high‐affinity B cells following affinity maturation 109, 110. These B cells may then re‐enter the dark zone and undergo further round(s) of proliferation and somatic hypermutation, or alternatively become long‐lived memory B cells or differentiate into long‐lived plasma cells that typically migrate out of the lymph node (LN) to reside in the bone marrow or gut 106.…”

Section: T Follicular Helper Cells and Their Role In Bnab Inductionmentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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“…Activated B cells and Tfh cells that eventually move from the T‐B border into the follicle seed GCs in which GC‐Tfh cells promote the growth and survival of high‐affinity antibody producing GC B cells. At the same time, GC‐Tfh cells are thought to be a major driver of antibody affinity maturation by governing the positive selection of GC B cells with highest affinity for a given antigen (Allen et al , 2007; Victora et al , 2010; Liu et al , 2014a). …”

Section: Introductionmentioning

confidence: 99%

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

et al. 2016

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Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long‐term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4+ T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell‐intrinsic manner. Our data indicate that T cell‐expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell‐dependent B‐cell responses.

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Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter

Cited by 1,000 publications

References 74 publications

Cytoskeletal control of B cell responses to antigens

Cytoskeletal control of B cell responses to antigens

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

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