CD19 regulates B cell antigen receptor-mediated MHC class II antigen processing.
In B cells, the processing of antigens in the context of MHC class II molecules is initiated by the binding of antigen to the B cell antigen receptor (BCR). The BCR serves two roles in antigen processing, signaling for enhanced processing and endocytosing bound antigen. CD19 is a B cell surface molecule which has been demonstrated to function in modifying signals generated through the BCR, regulating T-cell dependent B-cell activation. Here we provide evidence that cross-linking CD19 selectively blocked BCR-mediated enhancement of the processing and presentation of antigens taken up by fluid pinocytosis. CD19 cross-linking also inhibited the processing and presentation of antigen internalized bound to the BCR by decreasing the degree and rate of internalization of the BCR and specific antigen and its trafficking to the class II peptide loading compartment. In contrast, CD19 cross-linking did not affect the rate of assembly of SDS-stable peptide class II complexes, indicating that CD19 cross-linking did not have a global effect on membrane trafficking in B cells but rather a selective effect on BCR trafficking. Thus, in addition to a direct role in modulating BCR signaling for B cell proliferation and differentiation, CD19 may indirectly influence B cell activation by regulating antigen processing and B cell interactions with helper T cells.
Wagle
N M
NM
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 North Campus Drive, Hogan 3-120, Evanston, IL 60208, USA.
Kim
J H
JH
Pierce
S K
SK
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003432:Cross-Linking Reagents; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010873:Pinocytosis / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D018941:Antigens, CD19; D003432:Cross-Linking Reagents; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell