Soluble and membrane-bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B lymphocytes.
In this study it is shown that both membrane-bound and soluble forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B cells. Activated B cells express the membrane-bound form of SLAM (mSLAM), the soluble (s) and the cytoplasmic (c) isoforms of SLAM, and the expression levels of mSLAM on B cells are rapidly upregulated after activation in vitro. Importantly, recombinant sSLAM and L cells transfected with mSLAM efficiently enhance B cell proliferation induced by anti-mu mAbs, anti-CD40 mAbs or Staphylococcus aureus Cowan I (SAC) in the presence or absence of IL-2, IL-4, IL-10, IL-12, or IL-15. sSLAM strongly enhances proliferation of both freshly isolated B cells and B cells derived from long-term in vitro cultures, indicating that SLAM acts not only during the initial phase of B cell activation but also during the expansion of preactivated B cells. In addition, sSLAM enhances production of IgM, IgG, and IgA by B cells activated by anti-CD40 mAbs. SLAM has recently been shown to be a high affinity self-ligand, and the present data suggest that signaling through homophilic SLAM-SLAM binding during B-B and B-T cell interactions enhances the expansion and differentiation of activated B cells.
Punnonen
J
J
Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Cocks
B G
BG
Carballido
J M
JM
Bennett
B
B
Peterson
D
D
Aversa
G
G
de Vries
J E
JE
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D006023:Glycoproteins / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013154:Spleen / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D007378:Interleukins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007041:Hypoxanthine Phosphoribosyltransferase