Stressed out? It turns out B cells need to be stressed to ramp up their metabolic capacity to make antibodies in response to infection. In the April issue of Nature Immunology, researchers at Harvard link the cellular stress response, known as the unfolded protein response, to the terminal differentiation of B cells to turn into antibody-producing plasma cells. The results provide new clues about how diseases, such as multiple myeloma, arise and may lead to new therapeutic targets.
Plasma cells are antibody factories, capable of synthesizing and secreting vast amounts of specific antibodies into the bloodstream. However, precursors of these cells need to be alerted to increase their production capacity. Glimcher and colleagues show B cells make small amounts of antibody, but these molecules fail to fold properly and signal the stress response. During this same period, B cells increase their expression of a gene called XBP-1, which is the master switch for plasma cell differentiation. However, the form of XBP-1 message produced in the absence of the stress response encodes a non-functional protein. The new data shows how this stress response triggers splicing of the XBP-1 message to encode the functional XBP-1 protein, which then turns on genes that are required for plasma cell differentiation and increased antibody production. Thus, aberrant activation of XBP-1 might contribute to the development of multiple myeloma, the malignant counterpart of plasma cells.
Laurie H. Glimcher
Depts. of Immunology & Infectious Diseases and Medicine
Harvard School of Public Health
Tel: + 617 432 0622
Additional contact for comment on paper:
Linda M. Hendershot
Department of Tumor Cell Biology
St. Jude Children's Research Hospital
Tel: +1 901 495 2475
Also available online.
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza
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