TY - JOUR
T1 - B lymphocytes differentially influence acute and chronic allograft rejection in mice
AU - DiLillo, David J.
AU - Griffiths, Robert
AU - Seshan, Surya V.
AU - Magro, Cynthia M.
AU - Ruiz, Phillip
AU - Coffman, Thomas M.
AU - Tedder, Thomas F.
PY - 2011/2/15
Y1 - 2011/2/15
N2 - The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD19 mAbs. Both CD20 and CD19 mAbs effectively depleted mature B cells, and CD19 mAb treatment depleted plasmablasts and some plasma cells. B cell depletion did not affect acute cardiac allograft rejection, although CD19 mAb treatment prevented allograftspecific IgG production. Strikingly, CD19 mAb treatment significantly reduced renal allograft rejection and abrogated allograftspecific IgG development, whereas CD20 mAb treatment did not. By contrast, B cell depletion exacerbated skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells, demonstrating that B cells can also negatively regulate allograft rejection. Thereby, B cells can either positively or negatively regulate allograft rejection depending on the nature of the allograft and the intensity of the rejection response. Moreover, CD19 mAb may represent a new approach for depleting both B cells and plasma cells to concomitantly impair T cell activation, inhibit the generation of new allograft-specific Abs, or reduce preexisting allograft-specific Ab levels in transplant patients.
AB - The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD19 mAbs. Both CD20 and CD19 mAbs effectively depleted mature B cells, and CD19 mAb treatment depleted plasmablasts and some plasma cells. B cell depletion did not affect acute cardiac allograft rejection, although CD19 mAb treatment prevented allograftspecific IgG production. Strikingly, CD19 mAb treatment significantly reduced renal allograft rejection and abrogated allograftspecific IgG development, whereas CD20 mAb treatment did not. By contrast, B cell depletion exacerbated skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells, demonstrating that B cells can also negatively regulate allograft rejection. Thereby, B cells can either positively or negatively regulate allograft rejection depending on the nature of the allograft and the intensity of the rejection response. Moreover, CD19 mAb may represent a new approach for depleting both B cells and plasma cells to concomitantly impair T cell activation, inhibit the generation of new allograft-specific Abs, or reduce preexisting allograft-specific Ab levels in transplant patients.
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U2 - 10.4049/jimmunol.1002983
DO - 10.4049/jimmunol.1002983
M3 - Article
C2 - 21248259
AN - SCOPUS:79951838633
VL - 186
SP - 2643
EP - 2654
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -