The long-term goal of this research is to investigate the mechanism in human B- and T-cell activation. Studies employing human peripheral blood, tonsil, and splenic lymphocytes indicate that Fc fragments derived from papain digestion, p'Fc fragments derived from plasmin digestion, aggregated immunoglobulin, and immune complexes are potent polyclonal activators. Studies designed to ascertain the cell-cell interaction requirements have revealed that both monocytes and T cells are required for the generation of polyclonal antibody. The role of the monocyte is to enzymatically cleave the Fc fragments into Fc subfragments which then induce Ig secretion. The role of the T cell is to secrete a B-cell differentiation factor (CDF) which in conjunction with Fc subfragments drive B cells to secrete Ig. The active region of the Fc fragment has been localized to approximately the first 24 residues of the CH?3? domain [Eu IgG?1? 335-258] of the molecule. Based on this sequence a 23 residue peptide (p23) was synthesized and found to be a potent lymphocyte activator. Fc fragments derived from a human IgG?1? myeloma protein are capable of augmenting the in vitro anti-SRBC response of human PBL. The addition of Fc to cultures of human PBL along with SRBC resulted in a pronounced enhancement of the primary in vitro anti-SRBC response. Augmentation of the immune response is mediated by Fc and not the result of an artifact due to the addition of extraneous protein to culture because neither intact IgG?1? nor Fab fragments possess any adjuvant properties. Over the past year, attempts have been made to establish a more relevant in vitro antigen-specific response model. We are currently investigating whether the in vitro antibody response to influenza by human PBL would be suitable. The choice of influenza as the test antigen is ideal since it represents an anamnestic response. (CS)
| Morgan, E L; Hobbs, M V; Thoman, M L et al. (1990) Induction of human B cell differentiation by Fc region activators. II. Stimulation of IL-6 production. J Immunol 144:2499-505 |
| Morgan, E L; Hobbs, M V; Noonan, D J et al. (1988) Induction of IL-1 secretion from human monocytes by Fc region subfragments of human IgG1. J Immunol 140:3014-20 |
| Morgan, E L (1987) The role of prostaglandins in C3a-mediated suppression of human in vitro polyclonal antibody responses. Clin Immunol Immunopathol 44:1-11 |
| Morgan, E L; Weigle, W O (1987) Biological activities residing in the Fc region of immunoglobulin. Adv Immunol 40:61-134 |
| Morgan, E L; Scheuer, W V; Hobbs, M V (1986) Antagonistic regulatory properties of the Fc region of immunoglobulin. Immunopharmacology 12:221-32 |
| Hobbs, M V; Morgan, E L; Weigle, W O (1985) Bifunctional lymphocyte regulation by human Fc gamma fragments and a synthetic peptide, p23, derived from the Fc region. Immunol Lett 9:201-6 |
