2014-05-01
CD20+ B Cell Depletion Alters T Cell Homing
Publication
Publication
Journal of Immunology , Volume 192 - Issue 9 p. 4242- 4253
Depleting mAbs against the pan B cell marker CD20 are remarkably effective in the treatment of autoimmune-mediated inflammatory disorders, but the underlying mechanisms are poorly defined. The primary objective of this study was to find a mechanistic explanation for the remarkable clinical effect of the anti-CD20 mAbs in a representative nonhuman primate autoimmune-mediated inflammatory disorder model, experimental autoimmune encephalomyelitis (EAE) in common marmosets, allowing detailed analysis of secondary lymphoid organs (SLO). We observed that the depletion of CD20+ B cells creates a less immunostimulatory environment in the SLO reflected by reduced expression of MHC class II, CD40, CD83, and CD80/CD86. APCs isolated from SLO of B cell-depleted EAE monkeys were also less responsive to mitogenic stimulation. The depleted B cell areas were replenished by T cells, of which the majority expressed CD127 (IL-7R) and CCR7. Such effects were not detected in EAE marmosets treated with mAb against BLyS or APRIL, where B cell depletion via withdrawal of essential survival cytokines was not associated with a marked clinical effect. We propose that at least part of the efficacy of anti-CD20 mAb therapy is attributable to the sustained CCR7 expression on T cells within SLO, limiting their release into the circulation. The Journal of Immunology, 2014, 192: 4242-4253.
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doi.org/10.4049/jimmunol.1303125, hdl.handle.net/1765/56982 | |
Journal of Immunology | |
Organisation | Department of Immunology |
Kap, Y., van Driel, N., Laman, J., Tak, P., & 't Hart, B. (2014). CD20+ B Cell Depletion Alters T Cell Homing. Journal of Immunology, 192(9), 4242–4253. doi:10.4049/jimmunol.1303125 |