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Understanding the role of B cells in T-cell alloimmunity would assist in the design of therapies to target B cells that inhibit not only antibody production but also T-cell immunity for lasting allograft survival. Several functions of B cells such as antigen http://www.selleckchem.com/products/AC-220.html presentation, costimulation and cytokine production can modulate T-cell differentiation and cellular immunity (35�C38). It has been shown that in the absence of antigen presentation by B cells, CD4 T-cell activation and alloantibody production were impaired resulting in delayed heart but not skin allograft rejection (39). However, it was not clear whether B cells had any impact on alloreactive T-cell memory. We studied the development of CD4 and CD8 memory T cells in B-cell-deficient and B-cell-competent hosts after allogeneic skin transplantation. We report that in the absence of B cells, CD4 and CD8 T cells differentiate into alloreactive effectors but their development into memory T cells is impaired resulting in decreased numbers of alloreactive memory T cells. We find that B cells promote proliferation of activated CD4 T cells and survival of CD8 T cells leading to increased numbers of memory T cells, and thus, contribute to the quantitative advantage of T-cell memory. C57BL/6 (CD45.2, H-2b; hereafter wt), B6.SJL-Ptprca Pepcb/BoyJ (CD45.1, H-2b; hereafter CD45.1), B6.129S2-Igh-6tm1Cgn/J (CD45.2, H-2b; hereafter ��MT) (40) and BALB/c (H-2d) mice were purchased from The Jackson Laboratory http://www.selleckchem.com/products/nutlin-3a.html (Bar Harbor, ME). All animals were maintained under SPF conditions and procedures were performed as per IACUC guidelines. Partial thickness skin transplantation was performed using BALB/c donor abdominal skin (41,42). Skin grafts were monitored daily and rejection was defined as >95% graft necrosis. In some experiments, allograft recipients were treated with donor specific transfusion (DST) (BALB/c splenocytes, 2 �� 107, day 0) and anti-CD40L (MR1, 1 mg, days 0, 7, 14) (Bio X Cell, West Lebanon, NH). Log-rank http://www.selleck.cn/products/Romidepsin-FK228.html test (Graphpad prism 4.0, Graphpad Software, Inc., La Jolla, CA) was used to assess differences in allograft survival and p-value of