SIGNAL-TRANSDUCTION BY B-CELLS AND T-CELLS EARLY AFTER BONE-MARROW TRANSPLANTATION - B-CELL CALCIUM FLUX RESPONSES ARE INTACT WHEREAS LACK OF CD4 CELLS ACCOUNTS FOR IMPAIRED T-CELL RESPONSES

We previously found that intracellular ionized calcium ([Ca2+]i) flux responses after anti-CDS crosslinking of CD3/TCR on T cells from allog eneic and autologous bone marrow transplant (BMT) recipients were impa ired, Yamagami et al. J Clin Invest 1990; 86: 1347-1351, In contrast t o the earlier study, this study focuses on identifying the T cell subs et(s) responsible for the defects and determining if B cell responses are defective in BMT recipients early after BMT, In 37 recipients afte r anti-CD3 stimulation of PBL, a mean of 25.9% responding T cells was observed, This was significantly lower than the mean of 43.6% respondi ng T cells in PBL from 21 normals (P < 0.001), The proportion of respo nding T cells in PBL (T PBL) increased in the recipients with time aft er BMT, By 6 months after BMT, the mean percent of responding T PBL ap proached the normal range, On the other hand, a mean of 8.1% respondin g B cells in anti-IgM crosslinked PBL from 24 recipients was not diffe rent from the mean of 7.4% responding B cells in anti-IgM crosslinked PBL from 16 normals (P = 0.6), Four color flow cytometry was used to i dentify subpopulations of lymphocytes. Enriched B cells were tested by gating out CD3(+) and CD56(+) cells to confirm the results of unfract ionated PBL, In 8 recipients, the mean percent responding B cells was 36.6% and was not different from 6 normals (mean = 41.0%), Although th e mean percent responding CD4(+) and CD8(+) cells in recipients was no t different from the controls, the absolute number of responding CD4() cells (67/mm(3)) from 13 recipients was significantly lower than tha t (244/mm(3)) seen for 9 controls (P = 0.003), In contrast, the absolu te numbers of responding CD8(+) cells (304/mm(3)) were not different f rom that (163/mm(3)) seen for the same controls (P = 0.28), The data s how that impaired recipient T cell responses are due to low absolute n umbers of CD4(+) cells and not due to the inability of CD4(+) cells to respond to anti-CD3 crosslinking. Signal transduction by recipient B cells was in the normal range. This strongly suggests that defective B cell functions mag be due, in part, to delayed reconstitution of CD4( +) cells after marrow transplantation.