Aborted Germinal Center Reactions and B Cell Memory by Follicular T Cells Specific for a B Cell Receptor V Region Peptide

The B cell receptors (BCRs) for antigen express variable (V) regions that are enormously diverse, thus serving as markers on individual B cells. V region-derived idiotypic (Id) peptides can be displayed as pId:MHCII complexes on B cells for recognition by CD4+T cells. It is not known if naive B cells spontaneously display pId:MHCII in vivo or if BCR ligation is required for expression, thereby enabling collaboration between Id+B cells and Id-specific T cells. Here, using a mouse model, we show that naive B cells do not express readily detectable levels of pId:MHCII. However, BCR ligation by Ag dramatically increases physical display of pId:MHCII, leading to activation of Id-specific CD4+T cells, extrafollicular T–B cell collaboration and some germinal center formation, and production of Id+IgG. Besides having implications for immune regulation, the results may explain how persistent activation of self-reactive B cells induces the development of autoimmune diseases and B cell lymphomas.

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Faculty Opinions recommendation of B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737033557.793568970 ◽

2019 ◽

Author(s):

Jim Drake

Keyword(s):

T Cells ◽

B Cell ◽

Mhc Class Ii ◽

Cell Receptor ◽

Class Ii ◽

B Cell Receptor ◽

V Region ◽

Receptor Ligation ◽

Mhc Class Ii Molecules

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IFN-γ–Producing CD4+T Cells Promote Generation of Protective Germinal Center–Derived IgM+B Cell Memory againstSalmonellaTyphi

The Journal of Immunology ◽

10.4049/jimmunol.1302526 ◽

2014 ◽

Vol 192 (11) ◽

pp. 5192-5200 ◽

Cited By ~ 25

Author(s):

Christian Perez-Shibayama ◽

Cristina Gil-Cruz ◽

Rodolfo Pastelin-Palacios ◽

Luisa Cervantes-Barragan ◽

Emiliano Hisaki ◽

...

Keyword(s):

T Cells ◽

B Cell ◽

Germinal Center ◽

Cd4 T Cells ◽

Cell Memory ◽

B Cell Memory ◽

Ifn Γ

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Faculty Opinions recommendation of Mcl-1 is essential for germinal center formation and B cell memory.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5640956.10675054 ◽

2011 ◽

Author(s):

Stefano Casola

Keyword(s):

B Cell ◽

Germinal Center ◽

Cell Memory ◽

B Cell Memory ◽

Germinal Center Formation

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Faculty Opinions recommendation of B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732604893.793573078 ◽

2020 ◽

Author(s):

Elizabeth Mellins ◽

Debopam Ghosh

Keyword(s):

Transcription Factor ◽

B Cells ◽

B Cell ◽

Germinal Center ◽

Cell Receptor ◽

B Cell Receptor ◽

Synergistic Induction ◽

Germinal Center B Cells

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T Cells Can Induce Somatic Mutation in B Cell Receptor-Engaged BL2 Burkitt’s Lymphoma Cells Independently of CD40-CD40 Ligand Interactions

The Journal of Immunology ◽

10.4049/jimmunol.164.3.1306 ◽

2000 ◽

Vol 164 (3) ◽

pp. 1306-1313 ◽

Cited By ~ 17

Author(s):

Stéphane Denépoux ◽

Nathalie Fournier ◽

Catherine Péronne ◽

Jacques Banchereau ◽

Serge Lebecque

Keyword(s):

T Cells ◽

B Cell ◽

Somatic Mutation ◽

Cell Receptor ◽

Cd40 Ligand ◽

Burkitt’S Lymphoma ◽

B Cell Receptor ◽

Lymphoma Cells ◽

Ligand Interactions ◽

Burkitt’S Lymphoma Cells

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B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells

Immunity ◽

10.1016/j.immuni.2018.01.008 ◽

2018 ◽

Vol 48 (2) ◽

pp. 313-326.e5 ◽

Cited By ~ 89

Author(s):

Wei Luo ◽

Florian Weisel ◽

Mark J. Shlomchik

Keyword(s):

Transcription Factor ◽

B Cells ◽

B Cell ◽

Germinal Center ◽

Cell Receptor ◽

B Cell Receptor ◽

Synergistic Induction ◽

Germinal Center B Cells

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Survival of human lymphoma cells requires B-cell receptor engagement by self-antigens

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1514944112 ◽

2015 ◽

Vol 112 (44) ◽

pp. 13447-13454 ◽

Cited By ~ 75

Author(s):

Ryan M. Young ◽

Tianyi Wu ◽

Roland Schmitz ◽

Moez Dawood ◽

Wenming Xiao ◽

...

Keyword(s):

B Cell ◽

B Cell Lymphoma ◽

Cell Receptor ◽

B Cell Receptor ◽

Large B Cell Lymphoma ◽

Bcr Signaling ◽

Human Lymphoma ◽

V Region ◽

Pathway Inhibition ◽

Self Antigens

The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) relies on chronic active B-cell receptor (BCR) signaling. BCR pathway inhibitors induce remissions in a subset of ABC DLBCL patients. BCR microclusters on the surface of ABC cells resemble those generated following antigen engagement of normal B cells. We speculated that binding of lymphoma BCRs to self-antigens initiates and maintains chronic active BCR signaling in ABC DLBCL. To assess whether antigenic engagement of the BCR is required for the ongoing survival of ABC cells, we developed isogenic ABC cells that differed solely with respect to the IgH V region of their BCRs. In competitive assays with wild-type cells, substitution of a heterologous V region impaired the survival of three ABC lines. The viability of one VH4-34+ ABC line and the ability of its BCR to bind to its own cell surface depended on V region residues that mediate the intrinsic autoreactivity of VH4-34 to self-glycoproteins. The BCR of another ABC line reacted with self-antigens in apoptotic debris, and the survival of a third ABC line was sustained by reactivity of its BCR to an idiotypic epitope in its own V region. Hence, a diverse set of self-antigens is responsible for maintaining the malignant survival of ABC DLBCL cells. IgH V regions used by the BCRs of ABC DLBCL biopsy samples varied in their ability to sustain survival of these ABC lines, suggesting a screening procedure to identify patients who might benefit from BCR pathway inhibition.

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