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-μ 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 antiCD40 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.

[1]  I. Stamenkovic,et al.  The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co‐stimulatory activity. , 1992, The EMBO journal.

[2]  R. Flavell,et al.  Mice deficient for the CD40 ligand. , 1994, Immunity.

[3]  A. Saxon,et al.  CD58 (LFA-3) stimulation provides a signal for human isotype switching and IgE production distinct from CD40. , 1994, Journal of immunology.

[4]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[5]  W. Paul,et al.  Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. , 1987, Science.

[6]  R. Siliciano,et al.  Role of interaction of CD2 molecules with lymphocyte function-associated antigen 3 in T-cell recognition of nominal antigen. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Fauci,et al.  IL-6 and tumor necrosis factor-alpha. Autocrine and paracrine cytokines involved in B cell function. , 1991, Journal of immunology.

[8]  T. Taniguchi,et al.  Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin , 1986, Nature.

[9]  C. Morimoto,et al.  CD27-CD70 interactions regulate B-cell activation by T cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Banchereau,et al.  Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Banchereau,et al.  Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10 , 1993, The Journal of experimental medicine.

[12]  R J Armitage,et al.  Humoral immune responses in CD40 ligand-deficient mice , 1994, The Journal of experimental medicine.

[13]  M. Bennett,et al.  Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells. , 1993, Journal of immunology.

[14]  C. Snapper.  Cytokine regulation of humoral immunity : basic and clinical aspects , 1996 .

[15]  E. Clark,et al.  Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[16]  W. Paul,et al.  Lymphocyte responses and cytokines , 1994, Cell.

[17]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[18]  E. Clark,et al.  Molecular and biological characterization of a murine ligand for CD40 , 1992, Nature.

[19]  Klaus Rajewsky,et al.  Impairment of T-cell-dependent B-cell responses and B-l cell development in CD19-deficient mice , 1995, Nature.

[20]  J. D. de Vries,et al.  Characterization of a novel CD2+ human thymic B cell subset. , 1993, Journal of immunology.

[21]  E. Maggi,et al.  Membrane tumour necrosis factor-α is involved in the polyclonal B-cell activation induced by HIV-infected human T cells , 1993, Nature.

[22]  J. Banchereau,et al.  Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. , 1991, Science.

[23]  M. Filbin,et al.  The cytoplasmic domain of the myelin P0 protein influences the adhesive interactions of its extracellular domain , 1994, The Journal of cell biology.

[24]  P. Bossù,et al.  T cell surface molecules regulating noncognate B lymphocyte activation. Role of CD2 and LFA-1. , 1992, Journal of immunology.

[25]  R. Coffman,et al.  TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. , 1989, Annual review of immunology.

[26]  R. de Waal Malefyt,et al.  IL-13 induces proliferation and differentiation of human B cells activated by the CD40 ligand. , 1993, International immunology.

[27]  I. Stamenkovic,et al.  Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  B. Cocks,et al.  A novel receptor involved in T-cell activation , 1995, Nature.

[29]  H. Mikawa,et al.  Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells , 1992, The Journal of experimental medicine.

[30]  A. Fauci,et al.  Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function , 1985, The Journal of experimental medicine.

[31]  J. C. Pratt,et al.  Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein , 1985, Nature.

[32]  J. Bajorath,et al.  The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome , 1993, Cell.

[33]  J. Belmont,et al.  CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome , 1993, Science.

[34]  Michael Loran Dustin,et al.  The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3 , 1987, Nature.

[35]  J. Strominger,et al.  Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[36]  T. Pawson,et al.  SH2 domains recognize specific phosphopeptide sequences , 1993, Cell.

[37]  M. Kimoto,et al.  Expression of the CD2 molecule on human B lymphoid progenitors. , 1992, International immunology.

[38]  A. Fischer,et al.  CD40 ligand mutations in X-linked immunodeficiency with hyper-IgM , 1993, Nature.

[39]  A. Simon,et al.  Divergent T-cell cytokine patterns in inflammatory arthritis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. de Waal Malefyt,et al.  Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[41]  C. Maliszewski,et al.  Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion , 1992, The Journal of experimental medicine.

[42]  E. Reinherz,et al.  An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein , 1984, Cell.

[43]  G. Aversa,et al.  The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation , 1993, The Journal of experimental medicine.

[44]  A. Fauci,et al.  Direct effect of interleukin 2 on the differentiation of human B cells which have not been preactivated in vitro , 1985, European journal of immunology.

[45]  L. Davis,et al.  Elevated Th1- or Th0-like cytokine mRNA in peripheral circulation of patients with rheumatoid arthritis. Modulation by treatment with anti-ICAM-1 correlates with clinical benefit. , 1995, Journal of immunology.

[46]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[47]  Hong Wang,et al.  Cytokine Gene Profile in Circulating Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus: Increased Interleukin-2 but not Interleukin-4 mRNA , 1994, Lupus.

[48]  E. Whitehorn,et al.  Ligand binding kinetics of IL-2 and IL-15 to heteromers formed by extracellular domains of the three IL-2 receptor subunits. , 1995, International immunology.

[49]  T. Tursz,et al.  Epstein-Barr virus-containing B-cell line produces an interleukin 1 that it uses as a growth factor. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Jeffrey A. Ledbetter,et al.  How B and T cells talk to each other , 1994, Nature.

[51]  A. Fischer,et al.  T cell clones from an X-linked hyper-immunoglobulin (IgM) patient induce IgE synthesis in vitro despite expression of nonfunctional CD40 ligand , 1994, The Journal of experimental medicine.

[52]  S. Davis,et al.  The structure and ligand interactions of CD2: implications for T-cell function. , 1996, Immunology today.

[53]  Z. Estrov,et al.  Lymphotoxin is an autocrine growth factor for Epstein-Barr virus- infected B cell lines , 1993, The Journal of experimental medicine.