Antigens varying in affinity for the B cell receptor induce differential B lymphocyte responses.
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 gamma1 transcripts, and B cell production of interleukin (IL) 2 and interferon gamma 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 Igalpha, 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.
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
V
V
Kouskoff
S
S
Famiglietti
G
G
Lacaud
P
P
Lang
J E
JE
Rider
B K
BK
Kay
J C
JC
Cambier
D
D
Nemazee
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004792:Enzyme Precursors / Q000378:metabolism; D006183:H-2 Antigens / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000502:physiology
D000941:Antigens; D019013:CD40 Antigens; D016207:Cytokines; D004792:Enzyme Precursors; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D002118:Calcium