Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells.
Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Ana M
AM
Avalos
Angelina M
AM
Bilate
Martin D
MD
Witte
Albert K
AK
Tai
Jiang
J
He
Maria P
MP
Frushicheva
Peter D
PD
Thill
Friederike
F
Meyer-Wentrup
Christopher S
CS
Theile
Arup K
AK
Chakraborty
Xiaowei
X
Zhuang
Hidde L
HL
Ploegh
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D007108:Immune Tolerance; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D055503:Protein Multimerization / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D000939:Epitopes; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D010047:Ovalbumin