Distinct Sequences in the Cytoplasmic Domain of Complement Receptor 2 Are Involved in Antigen Internalization and Presentation

Abstract

B cells express randomly rearranged surface Ig that forms part of a multiprotein complex known as the B cell receptor (BCR). Recognition of Ag via this receptor results in its capture, internalization, proteolysis and presentation to CD4+ T cells. The recognition of Ag by CD4+ T cells is critical for the selection of individual B cells, leading to the eventual secretion of a high affinity version of the BCR as an effective circulating Ab. B cells also express other receptors that recognize Ags associated with components of innate immunity. One of these receptors, CR2, binds Ags coated with activated complement components. Studies have shown that cross-linking CR2 and the BCR with complement-tagged Ags leads to enhanced Ag presentation by B cells. In addition, Ags targeted to B cell CR2 in the absence of BCR coligation are also efficiently presented to T cells. In this report, we identify several distinct sequences within the cytoplasmic domain of mouse CR2 (mCR2) that are essential for mCR2-mediated Ag presentation in both the presence and the absence of BCR cross-linking. The finding that distinct sequences in the cytoplasmic domain of mCR2 are essential for BCR-independent Ag presentation leads us to propose a novel role for CR2.

The Role of Complement in Immune and Autoimmune Responses

“…Consistent with this observation is the finding that attachment of C3b to the heavy chain of murine IgG results in a 100-fold reduction in the amount of IgG required for human B cell lines to stimulate heavy chain-specific T cell clones, without enhancing antigen presentation to light chain-specific T cell clones [106]. It is noteworthy that CD21 may be able to promote antigen presentation in non-specific B cells, without assistance from BCR [107]. Internalisation of antigen by CD21, is apparently steered by distinct amino acid sequences in the short cytoplasmic tail of CD21 to MHC class II-containing compartments different from those to which BCR-antigen complexes are delivered [107,108].…”

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4+ T helper type 1 subset differentiation

“…As B cells have low phagocytic capacity, the BCR 5,6,25,33 in combination with innate antigen receptors, 37 is crucial for efficient APC function. Until recently, cognate B cell/T cell interactions were thought to limit the differentiation of only antigenpresenting B cells into antibody-secreting cells 52 and antigen-specific memory B cells.…”

“…37 Aggrecan, isolated from bovine nasal cartilage, was purified using a modified protocol. 38 Briefly, following dissection and soft-tissue removal, septa were washed in PBS, cut into 2-mm 3 fragments, homogenized (3 · 15 seconds) in 50 mM sodium acetate, pH 6Á0, 4 M guanidine hydrochloride, 10 mM EDTA, 2 mM PMSF, 5 mM benzamidineHCl, 0Á1 mM 6-aminohexanoic acid at 100 mg cartilage/ ml and incubated for 60 hr at 4°.…”

Robust T-cell stimulation by Epstein-Barr virus–transformed B cells after antigen targeting to DEC-205

“…Apart from the BCR, only the complement receptor 2 (CR2 or CD21) and the Fc␥ receptor II have been suggested to lead to efficient antigen processing for MHC class II presentation. [16][17][18] Thus, it remains unclear whether antigen targeting to certain endocytic receptors could harness both DC priming and amplification of T-cell responses by virus or otherwise activated B cells at the same time.…”