Recipient B Cells Are Not Required for Graft-Versus-Host Disease Induction

muMT recipients of donor CD8 cells have less weight loss than do wild-type recipients of CD8 cells. Wild-type B6 and B6 muMT mice were irradiated and reconstituted with TCD C3H.SW BM (5 mice per group) with or without 2-3 × 10⁶ purified C3H.SW CD8⁺ T cells (13-15 mice/group). Data are shown from 3 independent experiments. †Indicates days in which P < .05, comparing either B6 or B6 muMT CD8 recipients with the corresponding BM alone group. ^∗ Indicates days in which the B6 CD8-recipient group had significantly more weight loss (P < .05) than did the muMT CD8-recipient group.

muMT recipients of donor CD8 cells develop histologic GVHD. Shown are the combined pathology scores from 3 independent experiments. Each circle is the score of an individual mouse; horizontal bars are mean values. P < .0001 comparing liver scores in wt or muMT CD8 recipients compared to the respective BM alone controls. P < .05 comparing ear scores in wt or muMT CD8 recipients compared to the respective BM alone controls. P = .02 and P = .12 comparing colon scores in wt and muMT CD8 recipients (respectively) to the appropriate BM alone control. P = .08, P = .55, and P = .34 comparing liver, ear, and colon scores (respectively) in wt CD8 recipients to those in muMT CD8 recipients.

Similar GVHD develops in anti-CD20 and control-treated CD8 recipients. (A) On day −14, mice received 200 μg anti-mouse CD20 or control. Some of these mice were irradiated on day 0 (IR) and all were sacrificed on day +1 postirradiation (which was day +16 after antibody treatment) to quantitate spleen and lymph node (LN) B cells. Three mice per group were analyzed; however, sufficient LN cells for analysis could only be obtained in 2/3 anti-CD20-treated mice and in 1/3 anti-CD20 and irradiated mice. Each symbol is data from an individual mouse. Horizontal lines are mean values. (B) Percent weight loss. Data combined from 2 experiments with similar results. P < .04 comparing weight change of anti-CD20 or isotype CD8 recipients with BM alone controls from days +6 and +11 onward, respectively. Weight change of anti-CD20 and control CD8 recipients did not differ at any measurement. (C) Skin disease incidence. Data from the 1 of 2 experiments in which significant clinical skin disease developed. P < .05 comparing anti-CD20 or control-treated CD8 recipients with the respective BM alone control. Incidences of skin disease in anti-CD20 and control IgG-treated CD8-recipients did not significantly differ. (D) Liver and colon pathology scores are shown for data combined from 2 experiments. P = .41 comparing colon or liver pathology in isotype to that in anti-CD20 CD8 recipients. P < .031 comparing colon GVHD in isotype or anti-CD20-treated CD8 recipients to the appropriate bone marrow only control. P < .0007 comparing liver GVHD in isotype or anti-CD20-treated CD8 recipients versus the bone marrow only control. Skin pathology is shown for the 1 (of 2 total) experiments with clinical skin GVHD. P = .22 comparing skin pathology in anti-CD20 versus isotype-treated CD8 recipients.

B cell-deficient JhD BALB/c recipients of donor B10.D2 spleen cells develop GVHD. JhD BALB/c or wild-type BALB/c recipients were irradiated and reconstituted with T cell-depleted B10.D2 BM (4 mice/group) without or with 10⁷ B10.D2 spleen cells (10-11 mice per group). Shown are results from 2 independent experiments. All statistical comparisons are between JhD and wild-type recipients of donor spleen cells. Experiment 1 data are in A, B, and C: incidence of clinical skin disease, A; clinical skin score, B (^∗P < .03); weight change, C (^∗P < .03). Experiment 2 data are in D, E, and F: incidence of clinical skin disease, D (^∗P < .05); clinical skin score, E (^∗P < .05 at day 26 only); weight change, F (^∗P < .006 at all time points beginning on day +17).