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Second signals rescue B cells from activation-induced mitochondrial dysfunction and death.

Abstract：

:B cells are activated by two temporally distinct signals, the first provided by the binding of antigen to the B cell antigen receptor (BCR), and the second provided by helper T cells. Here we found that B cells responded to antigen by rapidly increasing their metabolic activity, including both oxidative phosphorylation and glycolysis. In the absence of a second signal, B cells progressively lost mitochondrial function and glycolytic capacity, which led to apoptosis. Mitochondrial dysfunction was a result of the gradual accumulation of intracellular calcium through calcium response-activated calcium channels that, for approximately 9 h after the binding of B cell antigens, was preventable by either helper T cells or signaling via the receptor TLR9. Thus, BCR signaling seems to activate a metabolic program that imposes a limited time frame during which B cells either receive a second signal and survive or are eliminated.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Akkaya M,Traba J,Roesler AS,Miozzo P,Akkaya B,Theall BP,Sohn H,Pena M,Smelkinson M,Kabat J,Dahlstrom E,Dorward DW,Skinner J,Sack MN,Pierce SK

doi

10.1038/s41590-018-0156-5

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

871-884

issue

8

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-018-0156-5

journal_volume

19

pub_type

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