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Establishing the molecular mechanisms of B cell receptor internalization
Author(s) -
McCabe Kathleen O.,
Yelton Allison,
Drake Lisa,
Drake James R.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1067.4
Subject(s) - internalization , endocytosis , b cell receptor , microbiology and biotechnology , breakpoint cluster region , clathrin , signal transducing adaptor protein , ligand (biochemistry) , chemistry , receptor , biology , signal transduction , antibody , b cell , biochemistry , immunology
The B cell receptor (BCR) is comprised of ligand binding (IgH/L) and signaling (CD79a/b) subunits and mediates the processing/presentation of bound antigen. Internalization of the BCR had been reported to occur both through clathrin‐coated pits (CCPs) and lipid rafts (LRs), although it is unclear which pathway predominates. Use of a previously described model, consisting of a CD32‐CD79b fusion protein, demonstrates that the cytoplasmic tail of CD79b contains one or more functional endocytosis motifs. Internalization is crosslinking‐dependent, recapitulating the behavior of the native BCR when ligated with an antibody against the variable region of the IgH/L subunit. CD79b contains an ITAM with two Yxx? motifs that may bind the clathrin adaptor AP‐2, suggesting CCPs may be involved in internalization. However, there is also an increased association between the BCR and LRs upon receptor crosslinking, implying that under certain circumstances, LR localization of the BCR may lead to internalization subsequent to signaling. Current work focuses on mutating the conserved ITAM residues of CD79b to disrupt these potential AP‐2 binding sites. Additionally, by visualizing the BCR in morphologically identifiable CCPs by electron microscopy or in LRs by sucrose fractionation, the primary mechanism of BCR internalization will be further established. Supported by NIH grant AI‐065773 to JRD.