Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells.

Centre for Rheumatology Research, Division of Medicine, University College London, London WC1E 6JF, UK.
Immunity (Impact Factor: 19.75). 03/2012; 36(3):477-90. DOI: 10.1016/j.immuni.2012.02.008
Source: PubMed

ABSTRACT B cells perform many immunological functions, including presenting lipid antigen to CD1d-restricted invariant natural killer T (iNKT) cells, known to contribute to maintaining tolerance in autoimmunity. Patients with systemic lupus erythematous (SLE) display dysregulated B cell responses and reduced peripheral iNKT cell frequencies. The significance of these defects and how they relate to SLE pathogenesis remain elusive. We report that B cells are essential for iNKT cell expansion and activation in healthy donors but fail to exert a similar effect in SLE patients. Defective B cell-mediated stimulation of iNKT cells in SLE patients was associated with altered CD1d recycling, a defect recapitulated in B cells from healthy donors after stimulation with interferon-α (IFN-α) and anti-immunoglobulin (Ig). iNKT cell number and function were restored in SLE patients responding to anti-CD20 treatment upon normalization of CD1d expression exclusively in repopulated immature B cells. We propose that healthy B cells are pivotal for iNKT cell homeostasis.

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Jun 4, 2014