Evidence for an Important Interaction Between a Complement-Derived CD21 Ligand on Follicular Dendritic Cells and CD21 on B Cells in the Initiation of IgG Responses

• Published in: The Journal of immunology (1950) Vol. 161; no. 9; pp. 4549 - 4554
• Main Authors: Qin, Dahui, Wu, Jiuhua, Carroll, Michael C, Burton, Gregory F, Szakal, Andras K, Tew, John G
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.1998
• Subjects: Animals; Antibody Formation; B-Lymphocytes - immunology; Complement C3 - deficiency; Complement C3 - genetics; Complement C3 - pharmacology; Complement C3 - physiology; Complement System Proteins - immunology; Dendritic Cells - immunology; Female; Immunoglobulin G - biosynthesis; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Receptors, Complement 3d - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.9.4549

The addition of Ags to mononuclear leukocyte cultures typically elicits modest Ab responses, implying that cosignals beyond those provided by T cells and macrophages may be needed. Recently, we reported that Ab responses could be dramatically enhanced (10-1000-fold) by the addition of follicular dendritic cells (FDC), suggesting that FDC may provide an important costimulatory signal. This result prompted a study of molecules involved in FDC-mediated enhancement of Ab responses stimulated by specific Ag with memory T and B cells or nonspecifically by the addition of LPS. In this study, we report evidence supporting the concept that FDC bear a ligand that engages complement receptor II (CR2 or CD21) on B cells and provides a critical cosignal for both Ag-specific and polyclonal responses. A blockade of the CR2 ligand on FDC by the use of soluble CR2 or a blockade of CR2 on B cells by use of CR2 knockout mice (or B cells with CR2 blocked) reduced Ab responses from the microg/ml to the ng/ml range (10-1000-fold reductions). FDC from C3 knockout mice, which cannot generate the CR2-binding fragments (iC3b, C3d, and C3dg), were unable to provide costimulatory activity, suggesting the CR2 ligand on FDC consists of C3 fragments. FDC trap complement-activating Ag-Ab complexes, and it appears that FDC present B cells with both specific Ag to engage B cell receptors and a CR2 ligand to engage B cell-CR2. In short, optimal induction of specific Ab responses appears to require the combination of specific Ag and costimulatory molecules from both T cells and FDC.