Structure and Function of the Complement Receptors, CR1 (CD35) and CR2 (CD21)

Ahearn, Joseph M.; Fearon, Douglas T.

doi:10.1016/s0065-2776(08)60654-9

Cited by 415 publications

(254 citation statements)

References 179 publications

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“…Natural IgM enhances the adaptive Ab response by promoting the formation of immune complexes containing activated C3 fragments (33). In addition, it is well known that administration of IgM or IgG around the time of Ag encounter enhances Ab responses to suboptimal Ag doses (34).…”

Section: Discussionmentioning

confidence: 99%

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter

Sumiya

Reilly

et al. 2007

The Journal of Immunology

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To investigate the role of mannose-binding lectin-A (MBL-A) in protection against infectious disease, MBL-A−/−-deficient mice were generated. Using a well-characterized mouse model of human filarial nematode infection, nematode survival and protective immune responses were tested in vivo. Blood-borne Brugia malayi microfilariae survived for significantly longer time periods in MBL-A−/− than in wild-type (WT) mice. However, no differences in either splenic cytokine responses or induction of leukocytes in the blood were observed. A profound abrogation of Ag-specific IgM levels was measured in B. malayi-infected MBL-A−/− mice, and some IgG isotypes were higher than those observed in WT animals. To establish whether there was a defect in Ab responses per se in MBL-A−/− mice or the effect was specific to filarial infection, we immunized these mice with OVA or a carbohydrate-free protein. Significantly, Ag-specific IgM responses were defective to both of these Ags, and Ag-specific IgG responses were largely unaffected. Furthermore, in naive mice, total IgM levels did not differ between MBL-A−/− and WT mice. This article describes the first demonstration that MBL-A may function independently of MBL-C and suggests that MBL-A, like other C-type lectins and members of the complement cascade, is intimately involved in the priming of the humoral Ab response.

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Section: Discussionmentioning

confidence: 99%

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter

Sumiya

Reilly

et al. 2007

The Journal of Immunology

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“…CR1, also expressed on monocytes, granulocytes and erythrocytes, mediates the removal of C3-coated immune complexes from the circulation by binding to C3b. CR2 is predominantly expressed on mature B cells and follicular dendritic cells [35,36] and serves as the primary receptor for C3dg and iC3b [37,38]. Blockade of CR2 with an mAb almost completely prevented the uptake of iC3b-coated microparticles by B cells.…”

Section: Discussionmentioning

confidence: 99%

Differential mechanisms of microparticle transfer toB cells and monocytes: anti‐inflammatory propertiesof microparticles

Köppler¹,

Cohen²,

Schlöndorff

et al. 2006

Eur J Immunol

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Microparticles are small vesicles released from the plasma membrane of various cell types independently of apoptosis or cell death, are transferred between cells, and carry membrane proteins from one cell to another. We have studied the mechanism of uptake of microparticles by monocytes and B cells. The transfer of microparticles to B cells was almost completely dependent on complement. Incubation of microparticles with serum resulted in opsonization of microparticles with the complement cleavage product iC3b. The subsequent transfer to B cells was mediated by the complement receptor CR2. The interaction between iC3b-opsonized microparticles and B cells reduced the activation of B cells as measured by expression of MHC class II, CD86 and CD25. In contrast, transfer of microparticles to monocytes was only partially complement dependent, but involved calcium and annexin V, and was found to change the cytokine profile of monocytes towards a reduced release of the pro-inflammatory cytokines GM-CSF and TNF-a and an increased release of the anti-inflammatory cytokine IL-10. These data show that microparticles are taken up by B cells and monocytes by different mechanisms and modulate the activation of monocytes and B cells towards an anti-inflammatory phenotype. Microparticles might be involved in counterbalancing pro-inflammatory signals arising from tissue injury or inflammation.

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“…Besides follicular dendritic cells, CD21 is expressed only on mature B lymphocytes [1]. This might suggest that EBV ¹ persons contain more immature B lymphocytes in their blood.…”

Section: Discussionmentioning

confidence: 99%

“…Structurally, it consists of 15 or 16 extracellular short consensus repeats (SCR) followed by a transmembrane domain and an intracytoplasmic region [1]. CD21 was described as a receptor for the envelope glycoprotein gp350/ 220 of the EBV [2] and also as a receptor for interferon-alpha (IFN-a) [3].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Epstein–Barr virus (EBV) receptor CD21 on peripheral B lymphocytes of long-term EBV− adults

Jabs

Paulsen

Wagner

et al. 1999

Clinical and Experimental Immunology

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SUMMARYPrimary infections with EBV are rarely observed after the age of 20. Some individuals even remain seronegative all their lives. Previously, a lack of EBV receptors on B cells of persistently EBV ¹ adults was described as a reason for long-term EBV-seronegativity. The present study examined the CD21 receptor status of 20 repeatedly EBV ¹ healthy adults and 32 EBV þ volunteers by means of flow cytometry. CD21 molecules on the surface of CD19 þ B cells were quantified using anti-IgG-coated microbeads. The percentage of CD19 þ /CD21 þ B lymphocytes was slightly lower in the peripheral blood of EBV ¹ donors, but the CD21 antibody binding capacity on CD19 þ B cells showed no significant differences between EBV ¹ and EBV þ adults. In vitro studies showed an equally good EBV transformability of peripheral B lymphocytes of EBV ¹ and EBV þ donors. Since HLA-DR was recently described as a co-receptor for EBV infection of B cells, we also determined HLA-DRB1 alleles in the EBV ¹ group. We found a significant negative association of EBV-seronegativity with HLA-DR13 in comparison with 111 healthy blood donors. In summary, a biologically significant lack of the EBV receptor CD21 on peripheral B lymphocytes of persistently EBV ¹ adults was excluded as a reason for long-term EBV-seronegativity.

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Structure and Function of the Complement Receptors, CR1 (CD35) and CR2 (CD21)

Cited by 415 publications

References 179 publications

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Differential mechanisms of microparticle transfer toB cells and monocytes: anti‐inflammatory propertiesof microparticles

Analysis of Epstein–Barr virus (EBV) receptor CD21 on peripheral B lymphocytes of long-term EBV− adults

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