IgG anti-tetanus toxoid antibody synthesis by human bone marrow. I. Two distinct populations of marrow B cells and functional differences between marrow and peripheral blood B cells.

This investigation uses a system for inducing and detecting anti-tetanus toxoid antibody (anti-TT) synthesis to study specific antibody (Ab) synthesis by bone marrow mononuclear cells (MC). We measured the amounts of anti-TT secreted and the number of B cells secreting antibody (Ab). The ELISA plaque detects single B cells secreting specific Ab. The results show that (1) spontaneous anti-TT secretion by MC is higher than spontaneous anti-TT secretion by peripheral blood lymphocytes (PBL) using an ELISA plaque (P less than 0.01); (2) spontaneous anti-TT production by MC correlated with the serum anti-TT titers as measured by an ELISA (r = 0.75, P = 0.005); (3) two types of marrow B cells were identified--one that spontaneously secretes anti-TT and another that produces anti-TT after TT-stimulation; (4) the frequency of anti-TT-secreting B cells is higher in MC than in PBL; (5) the amount of Ab secreted per marrow B cell is not different from that secreted by a peripheral B cell; and (6) marrow B cells could be induced to produce anti-TT in vitro up to 10 months without added cytokines. These results show that bone marrow is a major repository for differentiated B cells that spontaneously produce Abs to maintain circulating Abs titers and for memory B cells that can be induced to produce specific Ab.

Transfer of specific immunity in marrow recipients given HLA-mismatched, T cell-depleted, or HLA-identical marrow grafts.

The transfer of tetanus toxoid (TT) and diphtheria toxoid (DT) specific immunity was evaluated in 209 short-term (less than 120 days postgrafting) and 257 long-term (greater than 198 days postgrafting) non-boosted recipients after HLA-identical, HLA non-identical, and HLA-identical T cell-depleted marrow transplantation. TT or DT immunizations were not given to donors in the 6 months prior to transplant and the recipients received no immunizations post-transplantation. In 209 short-term recipients, 94% and 74% of recipients had detectable anti-TT and anti-DT titers respectively. In long-term recipients, 110 of 210 (52%) who received HLA-identical grafts, 17 of 38 (45%) who received HLA-non-identical grafts, and seven of seven (100%) who received HLA-identical T cell-depleted grafts had anti-TT titers; and 86 of 212 (40%) who received HLA-identical grafts, 11 of 38 (29%) who received HLA-non-identical grafts, and four of seven (57%) who received HLA-identical T cell-depleted grafts had anti-DT titers. When compared to non-boosted normal donor and control subjects, the magnitudes of anti-TT and anti-DT titers from the recipients were comparable to controls. These data show that transferred specific immunity is detectable in long-term recipients of T cell-depleted or HLA-non-identical grafts without immunizations of donors or recipients before or after transplantation.

The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting.

This investigation uses different polyclonal activators of in vitro immunoglobulin production to elicit immunoregulatory profiles of B cells, T cells, T4 cells, and T8 cells from 25 recipients (13 with and 12 without chronic graft-v-host disease [GVHD] ) after HLA-identical marrow transplantation for aplastic anemia or hematologic malignancy. Pokeweed mitogen, Epstein-Barr virus, herpes simplex type 1 virus, and tetanus toxoid were used to induce immunoglobulin production as measured by a plaque assay. Multiple defects in the various lymphoid subsets were found in both groups of patients. There was defective b cell function, lack of T cell or T4 cell subset helper activity, and increased T cell, T4 cell, or T8 cell suppressor activity after stimulation with the various activators. Inconsistent B, T, T4, and T8 cell functions in the marrow graft recipients provide evidence for (a) different functional groups of cells within each subset responsive to different polyclonal activators; (b) a spectrum of immune capabilities within each phenotype lineage; (c) different patterns of immune reconstitution for each lymphocyte subset after marrow grafting; and (d) chronic GVHD altering recovery of in vitro functional responses to the different polyclonal activators.