Taking Aim at B Cells

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Science  09 Jul 2004:
Vol. 305, Issue 5681, pp. 149
DOI: 10.1126/science.305.5681.149b

Immunotherapies for autoimmune diseases and malignancies that involve B cells have focused largely on the removal or inhibition of the offending cells. This tactic has already been effective in treating non-Hodgkin's lymphoma with Rituximab, a chimeric antibody directed at the B cell surface protein, CD20. Despite some success using this mode of therapy, the mechanisms by which B cells are targeted have not been clearly delineated.

To explore pathways in anti-CD20 therapy, Uchida et al.generated a panel of murine B cell-depleting antibodies to CD20. The complement system has been considered a prime mediator in anti-CD20 depletion, and, although all the antibodies could kill cells using complement in vitro, B cell depletion still occurred efficiently in complement-deficient mice. On the other hand, in mice lacking the Fc receptor (FcR) common γ-chain, which is used both in complement and cell-mediated cytotoxicity, depletion was significantly compromised. The mechanism of anti-CD20 treatment implicated by these results was confirmed by showing that B cell depletion failed to take place in mice after macrophages had been removed. Defining the roles of FcγR-mediated phagocytosis during B cell depletion by anti-CD20 should help refine immunotherapy of B cell- dependent diseases. [Also see related article on Science's STKE]SJS

J. Exp. Med. 199, 1659 (2004).

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