B-cell dysfunction following human bone marrow transplantation: functional-phenotypic dissociation in the early posttransplant period.
We investigated the defect in humoral immunity that occurs following bone marrow transplantation (BMT). B cells from BMT recipients were tested for their ability to undergo the sequential steps of activation (RNA synthesis on stimulation with anti-mu or PMA), proliferation (DNA synthesis on stimulation with anti-mu plus B cell growth factor [BCGF], phorbol myristate acetate [PMA], or Staphylococcus aureus Cowan I [SAC] strain bacteria) and differentiation (Ig synthesis stimulated by T cell replacing factor [TRF]). B-cell maturation-associated cell surface markers were simultaneously investigated. "Early" (less than 10 months) posttransplant patients demonstrated defective B-cell activation and also failed to undergo normal proliferation and differentiation. Despite their functional impairment, the early patients' B cells displayed an "activated" phenotype with increased proportions of B cells displaying CD23 (a BCGF receptor) and decreased proportions of Leu 8+ B cells. Furthermore, these patients were uniquely distinguished by the fact that their B cells only weakly (if at all) expressed the CD19 antigen. In contrast, B cells from "late" patients (greater than or equal to 10 months post-BMT) activated and proliferated normally and displayed a normal cell surface phenotype, yet were unable to differentiate to high rate Ig secretion with TRF. Our results suggest a phenotype/function dissociation in early posttransplant period. With time, B cells in BMT patients acquire a normal surface phenotype and can activate and proliferate normally, yet still demonstrate a block in terminal differentiation.
Kagan
J M
JM
Department of Medicine, UCLA School of Medicine, Los Angeles.
Champlin
R E
RE
Saxon
A
A
D000293:Adolescent; D000328:Adult; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015847:Interleukin-4; D007378:Interleukins / Q000032:analysis; D008213:Lymphocyte Activation; D010641:Phenotype; D011183:Postoperative Complications / Q000097:blood / Q000473:pathology
D000944:Antigens, Differentiation, B-Lymphocyte; D007378:Interleukins; D015847:Interleukin-4