Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation.
We explored the role of antigen valency in B cell receptor (BCR) activation and rearrangement of intracellular MHC class II compartments as factors that contribute to the efficacy of antigen presentation. Using primary B cells that express a hen egg lysozyme (HEL)-specific BCR, we found that oligomeric HEL more efficiently promoted both BCR activation and internalization than did monovalent HEL, although monovalent HEL, unlike monovalent Fab fragments of anti-Ig, readily triggered the BCR. Nonetheless, oligovalent ligation positions the BCR in a membrane microdomain that is distinct from one engaged in the course of monovalent ligation, as judged by detergent extraction of the BCR. Furthermore, oligovalent HEL induced more pronounced rearrangement of MHC class II-containing antigen-processing compartments. Using videomicroscopy we observed in real time the rearrangement of MHC class II compartments as well as delivery of antigen in primary B cells. The observed increase in rearrangement of MHC class II-positive compartments and the disposition of antigen-bound BCRs therein correlates with improved presentation of a HEL-derived epitope. Although monomeric HEL efficiently engages the BCR, presentation of HEL-derived epitopes is impaired compared to oligovalent antigens. This trait may help explain the known ability of soluble, disaggregated antigen to induce a state of B cell tolerance.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
You-Me
YM
Kim
Jennifer Yi-Jiun
JY
Pan
Gregory A
GA
Korbel
Victor
V
Peperzak
Marianne
M
Boes
Hidde L
HL
Ploegh
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D011947:Receptors, Antigen, B-Cell; D002784:Cholesterol; C421864:hen egg lysozyme; D009113:Muramidase; D002118:Calcium