B cell responses to a peptide epitope. IX. The kinetics of antigen binding differentially regulates costimulatory capacity of activated B cells.
We explore the possible mechanism by which association rates of Ag with activated B cells influences the ability of the latter to selectively recruit Th subsets. Our system used cocultures of Ag-activated B and T cells, where the Ag was a synthetic peptide, G41CT3. Restimulation was with either peptide G41CT3 or its analogue, G28CT3. Peptide G28CT3 has been previously shown to display a higher on rate, relative to the homologous peptide G41CT3, of binding to G41CT3-activated B cells. This difference in on rates was eventually exerted at the level of IFN-gamma, but not of IL-10, induction from T cells, with peptide G28CT3 proving more effective. However, various treatment regimens rendered peptide G41CT3 as potent as peptide G28CT3 at eliciting IFN-gamma responses from the above cultures. This included simultaneous treatment of B cells with peptide G41CT3 and the protein tyrosine kinase inhibitor tyrphostin. Alternatively, pretreatment of B cells with a peptide representing only the B cell epitope constituent of peptide G28CT3 (G28) was also equally effective. Subsequent experiments revealed that IFN-gamma production from activated T cells resulted from an engagement of CD28 by B7-1 on the B cell surface. Finally, the extent of cell surface B7-1 up-regulation on activated B cells was dependent on the on rate of Ag binding to the membrane-bound Ig receptor. Thus, cumulative results suggest that the kinetics of Ag binding to activated B cells can differentially regulate intracellular signaling. This influences selective costimulatory molecule expression, with its consequent effects on relative Th subset activation.
Vijayakrishnan
L
L
Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Natarajan
K
K
Manivel
V
V
Raisuddin
S
S
Rao
K V
KV
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D004791:Enzyme Inhibitors; D018985:Epitopes, B-Lymphocyte; D008562:Membrane Glycoproteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; D007371:Interferon-gamma