Editors' ChoiceImmunology

New connections: Reprogramming B cell metabolism

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Science Signaling  26 Jun 2018:
Vol. 11, Issue 536, eaau5589
DOI: 10.1126/scisignal.aau5589

Two key regulators of B cell metabolism are required for effective immune responses.

The secretion of antibodies by B cells of the adaptive immune system is important for the response to infection. Upon activation by antigen through a cognate B cell receptor (BCR), B cells can differentiate into antibody-secreting plasma cells or enter structures called germinal centers (GCs) within secondary lymphoid organs, where they undergo changes that lead to the production of higher affinity antibodies. These responses are energetically demanding. The β isoform of protein kinase C (PKCβ) is highly abundant in B cells and mediates proliferative signaling downstream of the BCR. Tsui et al. showed that in mice with PKCβ-deficient B cells, the formation of GCs and the generation of plasma cells were defective. PKCβ-deficient B cells were less efficient than wild-type B cells at presenting antigen to helper T cells, an important component of the GC response. In addition, loss of PKCβ in B cells reduced the activation of the energy-regulating kinase complex mTORC1, resulting in defective metabolism and mitochondrial remodeling, which led to impaired plasma cell differentiation. In the Science Signaling Archives, Mendoza et al. showed in mice that B cells lacking the GTPase R-Ras2 failed to proliferate and undergo the GC response. R-Ras2 was downstream of both the BCR and the costimulatory protein CD40. Loss of R-Ras2 in B cells inhibited activation of the PI3K-Akt-mTORC1 pathway, reduced the replication of mitochondrial DNA, and decreased the expression of genes required for glucose metabolism. Together, these studies highlight two important factors that mediate the metabolic reprogramming of B cells that is necessary to mount effective antibody responses.

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