Monoclonal antibody against the human peripheral lymph node homing receptor homologue (Leu 8) inhibits B cell differentiation but not B cell proliferation.
Previous studies have shown that a subpopulation of circulating human B cells expresses the Leu 8 peripheral lymph node homing receptor homologue and that these B cells are capable of producing Ig in response to staphylococcus A Cowan I (SAC). In the present study the effect of a signal delivered via the Leu 8 molecule (using anti-Leu 8 mAb) on B cells was examined. Initially, it was shown that immobilized anti-Leu 8 suppressed IgM and IgG secretion of B cells activated by SAC + IL-2 but not that by PWM-prestimulated B cells or B cells stimulated with PWM in the presence of CD4+, Leu 8- T cells (a source of helper cells). It was also shown that anti-Leu 8 did not suppress SAC + IL-2-stimulated B cell proliferation or expression of IL-2R alpha-chain or c-myc mRNA in B cells. The addition of T cells, monocytes, purified IL-2, rIL-1, rIL-6, or human B cell growth factor did not overcome the inhibitory effect of anti-Leu 8 on SAC-stimulated B cell Ig production, and the inhibitory effect of anti-Leu 8 was not blocked by anti-TGF-beta. Finally, inhibition of B cell differentiation occurred even when anti-Leu 8 was added up to 72 hrs after initiation of cell culture. Thus, anti-Leu 8 is unique among inhibitors of B cell function in that it can down-regulate immunoglobulin synthesis without affecting B cell proliferation. These findings suggest that a natural ligand for Leu 8 could affect not only homing of B cells, but also B cell differentiation.
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Y
Y
Murakawa
W
W
Strober
S P
SP
James
D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D019041:L-Selectin; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D015847:Interleukin-4