Murine macrophages lack expression of the Cr2‐145 (CR2) and Cr2‐190 (CR1) gene products

Martin, Brian K.; Weis, John H.

doi:10.1002/eji.1830231146

Cited by 24 publications

(17 citation statements)

References 29 publications

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“…Moreover, the TD response of FoB cells to the antigen TNP-KLH was found to be impaired in MZB1-deficient mice, suggesting a more general function of MZB1 in humoral immune responses. The reduced antibody titers in immunized Mzb1 fl/fl CD21-cre mice suggest a B-cell-intrinsic defect because CD21 is almost specifically expressed in B cells (Martin and Weis 1993;Kozono et al 1998). Moreover, the number of germinal center B cells was not altered in immunized Mzb1 fl/fl CD21-cre mice relative to Mzb1 +/+ CD21-cre control mice (data not shown).…”

Section: Discussionmentioning

confidence: 99%

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

et al. 2014

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MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1 -/-mice. A similar developmental block was observed in Mzb1 fl/fl mb1Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin m heavy chains (mHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with mHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of mHCs under conditions of ER stress.

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Section: Discussionmentioning

confidence: 99%

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

et al. 2014

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“…J774-33 cells were used in this study since they readily bind and phagocytose C. perfringens and other Gram-positive bacteria (O9Brien & Melville, 2000). J774 cells are known to express the scavenger receptor (Ding et al, 1998) and the Fc receptor (Martin & Weis, 1993) and some clones express the mannose receptor (Fiani et al, 1998). They also express the complement receptor CR3 (Hall et al, 1991), but not CR1 or CR2 (Martin & Weis, 1993).…”

Section: Discussionmentioning

confidence: 99%

Multiple effects on Clostridium perfringens binding, uptake and trafficking to lysosomes by inhibitors of macrophage phagocytosis receptors

O’Brien

Melville

2003

Microbiology

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Clostridium perfringens is a Gram-positive, anaerobic bacterium that is the most common cause of gas gangrene (clostridial myonecrosis) in humans. C. perfringens produces a variety of extracellular toxins that are thought to be the major virulence factors of the organism. However, C. perfringens has recently been shown to have the ability to survive in a murine macrophage-like cell line, J774-33, even under aerobic conditions. In J774-33 cells, C. perfringens can escape the phagosome and gain access to the cytoplasm. Since the receptor that is used for phagocytosis can determine the fate of an intracellular bacterium, we used a variety of inhibitors of specific receptors to identify those used by J774-33 cells to phagocytose C. perfringens. It was found that the scavenger receptor and mannose receptor(s) were involved in the phagocytosis of C. perfringens. In the presence of complement, the complement receptor (CR3) was also involved in the binding and/or uptake of C. perfringens. Since the receptor inhibition studies indicated that the scavenger receptor played a major role in phagocytosis, C. perfringens binding studies were performed with a Chinese hamster ovary (CHO) cell line expressing the mouse SR-A receptor. The cell line expressing the SR-A receptor showed a significant increase in C. perfringens binding in comparison to the non-transfected CHO cells. In the absence of opsonizing antibodies, the Fc receptor was not used to phagocytose C. perfringens. Forcing the macrophages to use a specific receptor by using combinations of different receptor inhibitors led to only a slight increase in co-localization of intracellular C. perfringens with the late endosome-lysosome marker LAMP-1. Carbohydrate analysis of C. perfringens strain 13 extracellular polysaccharide confirmed the presence of mannose and negatively charged residues of glucuronic acid, which may provide the moieties that promote binding to the mannose and scavenger receptors, respectively.

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“…Murine B cells and follicular dendritic cells of the spleen are the only two cell types that express CD21 (3). Murine T cells do not express CD21 (4).…”

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confidence: 99%

Yin Yang 1, Oct1, and NFAT-4 Form Repeating, Cyclosporin-Sensitive Regulatory Modules Within the Murine CD21 Intronic Control Region

Zabel

Wheeler

Weis

et al. 2002

The Journal of Immunology

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The murine complement receptor type 2 gene (Cr2/CD21) is expressed by murine B and follicular dendritic cells, but not murine T cells. We have previously shown that appropriate transcriptional control of the CD21 gene requires the CD21 promoter as well as intronic sequences. We have also demonstrated that altering chromatin structure by inhibiting histone deacetylases induces CD21 expression in murine T cells by increasing the accessibility of promoter and intronic regulatory elements. In this report, we identify seven distinct regulatory areas within the first intron of the murine CD21 gene that are conserved between mouse and human CD21 intronic sequences. EMSA competition and supershift analyses reveal the formation of multiple DNA-protein complexes at these sites that include Yin Yang 1, Oct1, and NFAT-4. NFAT-containing complexes were altered in B cells treated with the NFAT inhibitor cyclosporin A and correlated with a repression of CD21 gene transcription implicating NFAT transcriptional control. Functional data revealed that no single region conferred cell-specific reporter gene expression, but rather the entire CD21 regulatory element was required to confer cell-specific gene expression. Taken together, these data demonstrate the formation of repeating, overlapping regulatory modules, all of which are required to coordinately control the cell-specific expression of the murine CD21 gene. We propose a model in which Yin Yang 1 and Oct1 may recruit histone deacetylase to multiple sites in the CD21 intronic regulatory element in nonexpressing cells and NFAT either displaces this histone deacetylase or recruits a histone acetylase to allow the formation of a functional transcriptional complex in expressing cells.

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Murine macrophages lack expression of the Cr2‐145 (CR2) and Cr2‐190 (CR1) gene products

Cited by 24 publications

References 29 publications

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

Multiple effects on Clostridium perfringens binding, uptake and trafficking to lysosomes by inhibitors of macrophage phagocytosis receptors

Yin Yang 1, Oct1, and NFAT-4 Form Repeating, Cyclosporin-Sensitive Regulatory Modules Within the Murine CD21 Intronic Control Region

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