B Cells in Transplantation of Rat, Mouse, and Man
A new model system reported by Panzer and colleagues2 might help to address that question and, in doing so, help to reformulate lymphocyte biology. Panzer and colleagues asked whether and how B cells contribute to the early events after organ transplantation and did so using a new rat model rather than using established mouse models. Unmanipulated B cell–deficient mice reject organ allografts as quickly as wild type (WT) mice3,4; however, transplants in B cell– and T cell–deficient mice have far less ischemia-reperfusion and early dysfunction thought to be caused by natural antibodies and complement.5 To pursue this query further, the authors performed kidney transplants in B cell–deficient and WT rats and compared the function and pathology of kidney allografts on the seventh postoperative day.
The gene-targeted rats were probably not fully B cell deficient because targeting of mu heavy-chain exons does not preclude generation of some B cells capable of producing IgG or IgA (and indeed some IgG-producing cells were detected by enzyme-linked immunospot). However, the presence of some B cells probably allowed lymphoid organogenesis and T cell development to occur,1 without which some might question whether absence of B cells or aberrant T cells could explain whatever differences in outcome. Three clear and compelling findings emerged.
All transplants, 6 in WT and 5 in B cell–deficient rats, exhibited substantial early dysfunction. Transplants in WT rats had C4d deposits and more interstitial inflammation; B cell–deficient rats had increased expression of IL-10 mRNA in the spleen. Whether the early C4d and inflammation in WT and IL-10 in mutant rats will be found to presage rejection or absence thereof at later times remains to be seen; however, clearly none of these differences had an impact on graft function during the first week after transplantation.