Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

• Published in: The Journal of immunology (1950) Vol. 167; no. 11; pp. 6132 - 6139
• Main Authors: Blanca, Isaac R, Bere, Earl W, Young, Howard A, Ortaldo, John R
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.12.2001
• Subjects: Antibodies, Monoclonal - pharmacology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; CD40 Antigens - genetics; CD40 Antigens - metabolism; CD40 Antigens - physiology; CD40 Ligand - immunology; CD40 Ligand - metabolism; CD40 Ligand - physiology; CD5 Antigens - biosynthesis; Cell Adhesion - drug effects; Cell Adhesion - immunology; Cell Communication - drug effects; Cell Communication - immunology; Cell Separation; Cells, Cultured; Coculture Techniques; Fixatives - pharmacology; Glutaral - pharmacology; Humans; Immunization; Immunologic Memory; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukocyte Common Antigens - biosynthesis; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - pharmacology; Recombinant Fusion Proteins - pharmacology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.11.6132

NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of the ongoing Ab response. More recently, it has been suggested that NK cells have an important role in the outcome of autoimmune diseases. Here, we demonstrate that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. B cell activation by the NK cell is contact-dependent and rapid, suggesting an autocrine B cell-regulated process. This NK cell function is T cell-independent, requires an active cytoplasmic membrane, and is blocked by anti-CD40 ligand (anti-CD154) or CD40-mIg fusion protein, indicating a critical role for CD40-CD40 ligand interaction. Depletion studies also demonstrate that CD5+ B cells (autoreactive B-1 cells) and a heterogeneous population of CD27+ memory B cells play a critical role in the Ig response induced by NK cells. The existence of this novel mechanism of B cell activation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasia.