Analysis of MHC class II presentation of particulate antigens of B lymphocytes.
To generate Ab responses to most protein Ags, B cells must first degrade proteins in endocytic compartments and then display antigenic peptides bound to MHC class II molecules. T helper lymphocytes recognize these complexes and stimulate the B cell to synthesize Ab. Although Ab play a key role in host defense against bacteria, it is believed that B cells are incapable of internalizing particulate Ags. However, we find that B lymphoblastoid cell lines and LPS-activated B lymphocytes can present particulate Ag up to 10(5)-fold more efficiently compared with soluble Ag. Moreover, particulate Ags are presented efficiently by unstimulated B cells when they bind to surface Ig. In comparison to B cells, macrophages in general presented particulate Ags 10- to 1000-fold more efficiently and could also present Ag from particles of a much wider range of sizes. We document by ultrastructural and immunofluorescence analysis that B lymphoblastoid cell lines bind and internalize these particles. The internalization and presentation of the particulate Ag is inhibited by cytochalasin B. In contrast, a similar morphologic analysis of normal lymphocytes demonstrated that while Ag beads are bound to the cell surface, they are internalized only rarely. These results suggest there may be both surface and intracellular pathways for the presentation of particulate Ags by B cells. Interestingly, for both macrophages and B cells, the epitopes generated from particulate and soluble Ags were not identical quantitatively or qualitatively, indicating that there are differences in how these forms of Ag are processed and presented.
Vidard
L
L
Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Kovacsovics-Bankowski
M
M
Kraeft
S K
SK
Chen
L B
LB
Benacerraf
B
B
Rock
K L
KL
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D003571:Cytochalasin B / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010316:Particle Size; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D012995:Solubility
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; D003571:Cytochalasin B