Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement

Abstract

Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non- Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.

Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

“…B cells are rare in peripheral blood during the first months after HSCT and reach close to normal levels within 6-12 months [17]. The CDR3 immunoglobulin (Ig)M spectra, i.e.…”

“…Low numbers of recipient‐derived B cells can also be encountered during the first period after transplantation, especially after reduced intensity conditioning [25]. Because B cell‐depleted and non‐depleted bone marrow give similar reconstitution in patients who underwent intense myeloablative conditioning, pre‐existing mature B cells do not seem to play a major role long‐term [17,26,27]. Although only donor‐derived B cells circulate in blood, the maintenance of recipient‐derived serum antibodies several years after transplantation reflects the resistance and longevity of plasma cells [28–30].…”

“…Although mature B cells are efficiently depleted during conditioning, the levels of circulating IgG antibodies drop slowly [17,39]. This is due to the long half‐life of IgG in serum [40] and the survival of many plasma cells after myelodepletion [30].…”

Reconstitution of the immune system after hematopoietic stem cell transplantation in humans

“…This suggests that early posttransplant, the infused B cells contribute to the recipient B cell pool. However, there is also indirect evidence for the origin of B cells from stem cells, as supranormal amounts of B-cell precursors are frequently found in the marrow at 2-12 months after transplant, i.e., prior to the overshoot of circulating B cell counts above the normal adult range (125,(137)(138)(139), and in recipients of B cell-purged autologous marrow, the tempo of B-cell reconstitution is not slower than in the recipients of unmanipulated marrow (140)(141)(142). Thus, both B-cell-derived and stem-cell-derived B cells may coexist after grafting.…”