The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell–independent B cell proliferation, antibody secretion, induction of germline immunoglobulin γ1 transcripts, and B cell production of interleukin (IL) 2 and interferon γ responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40 signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at saturating ligand concentrations the ability of phage to stimulate some early signaling responses, such as Ca++ mobilization and tyrosine phosphorylation of syk or Igα, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signaling by antigen determines whether an antibody response will be T independent or dependent is discussed.
Skip Nav Destination
Article navigation
19 October 1998
Article|
October 19 1998
Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
Valerie Kouskoff,
Valerie Kouskoff
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
Sara Famiglietti,
Sara Famiglietti
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
Georges Lacaud,
Georges Lacaud
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
Paul Lang,
Paul Lang
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
James E. Rider,
James E. Rider
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
Brian K. Kay,
Brian K. Kay
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
John C. Cambier,
John C. Cambier
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
David Nemazee
David Nemazee
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Search for other works by this author on:
Valerie Kouskoff
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Sara Famiglietti
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Georges Lacaud
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Paul Lang
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
James E. Rider
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Brian K. Kay
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
John C. Cambier
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
David Nemazee
From the *Department of Pediatrics and the ‡Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; the §Department of Immunology, University of Colorado Health Science Center, Denver, Colorado 80220; ‖EISAI London Research Laboratories, University College of London, London WC1E 6BT; the ¶Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and the **Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706
Address correspondence to David Nemazee, The Scripps Research Institute, 10550 N. Torrey Pines Rd., Mail Drop TPC 29, La Jolla, CA 92037. Phone: 619-784-9529; Fax: 619-784-8805; E-mail: nemazee @scripps.edu
Received:
July 14 1998
Revision Received:
August 04 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (8): 1453–1464.
Article history
Received:
July 14 1998
Revision Received:
August 04 1998
Citation
Valerie Kouskoff, Sara Famiglietti, Georges Lacaud, Paul Lang, James E. Rider, Brian K. Kay, John C. Cambier, David Nemazee; Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses . J Exp Med 19 October 1998; 188 (8): 1453–1464. doi: https://doi.org/10.1084/jem.188.8.1453
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
