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In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb)
Author(s) -
Harper D.,
Gollackner B.,
Xu Y.,
Calderhead D.,
Ryan D.,
Li W.,
Chang J.,
Wu C.,
Moran K.,
Latinne D.,
Bazin H.,
WhiteScharf M. E.,
Cooper D. K. C.,
Awwad M.
Publication year - 2004
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2004.00086.x
Subject(s) - monoclonal antibody , elispot , biology , in vivo , antibody , microbiology and biotechnology , bone marrow , population , in vitro , xenotransplantation , plasma cell , immunology , antigen , transplantation , medicine , biochemistry , environmental health , cd8
Natural antibodies (Abs), predominately anti‐Gal α 1–3Gal (Gal) Abs, in non‐human primates and human beings present a major hurdle to successful pig‐to‐primate xenotransplantation. Attempts to inhibit anti‐Gal Ab production in naïve baboons using non‐specific immunosuppressive or B cell‐specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA‐DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti‐Gal Ab and total immunoglobulin (Ig)‐secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti‐CD154 mAb to inhibit sensitization, anti‐rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme‐linked spot‐forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti‐Gal Ab was observed. W5 mAb did not cause complete inhibition of anti‐Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments.