Murine complement receptor 1 is required for germinal center B cell maintenance but not initiation

Donius, Luke R.; Weis, Janis J.; Weis, John H.

doi:10.1016/j.imbio.2014.02.007

Cited by 5 publications

(3 citation statements)

References 32 publications

(51 reference statements)

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“…Although CAF01 can elicit fully established GCs in neonates (30) its effect on neonatal FDC-M2 + FDC maturation has not been reported. Others have proposed the role of FDC-M1 + FDCs (56, 57) and CR1 (56, 58) in the organization of B cell follicles and maintenance of GC in early life, whereas our previous work did not indicate that they were limiting factors for FDC network maturation (9). In agreement with our results, i.p.…”

Section: Discussioncontrasting

confidence: 79%

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

et al. 2019

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Immaturity of the immune system contributes to poor vaccine responses in early life. Germinal center (GC) activation is limited due to poorly developed follicular dendritic cells (FDC), causing generation of few antibody-secreting cells (ASCs) with limited survival and transient antibody responses. Herein, we compared the potential of five adjuvants, namely LT-K63, mmCT, MF59, IC31, and alum to overcome limitations of the neonatal immune system and to enhance and prolong responses of neonatal mice to a pneumococcal conjugate vaccine Pnc1-TT. The adjuvants LT-K63, mmCT, MF59, and IC31 significantly enhanced GC formation and FDC maturation in neonatal mice when co-administered with Pnc1-TT. This enhanced GC induction correlated with significantly enhanced vaccine-specific ASCs by LT-K63, mmCT, and MF59 in spleen 14 days after immunization. Furthermore, mmCT, MF59, and IC31 prolonged the induction of vaccine-specific ASCs in spleen and increased their persistence in bone marrow up to 9 weeks after immunization, as previously shown for LT-K63. Accordingly, serum Abs persisted above protective levels against pneumococcal bacteremia and pneumonia. In contrast, alum only enhanced the primary induction of vaccine-specific IgG Abs, which was transient. Our comparative study demonstrated that, in contrast to alum, LT-K63, mmCT, MF59, and IC31 can overcome limitations of the neonatal immune system and enhance both induction and persistence of protective immune response when administered with Pnc1-TT. These adjuvants are promising candidates for early life vaccination.

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Section: Discussioncontrasting

confidence: 79%

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

et al. 2019

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“…CR2 is expressed on B cells and follicular dendritic cells, whereas CR1 is expressed on various kinds of cells, including macrophages, erythrocytes, B and T lymphocytes 31 . CR1 and 2 bind to C3b and C3d, respectively, and were shown to play a pivotal role in innate and adaptive immunity, involving phagocytosis, complement regulation and maintenance of germinal center B cells and memory B cells 32 , 33 . Moreover, Donius et al .…”

Section: Discussionmentioning

confidence: 99%

Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance

Itakura

Sato

Ito

et al. 2017

Sci Rep

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Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wild-type mice, Spred2−/− mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP. The MEK inhibitor U0126 significantly reduced LPS-induced chemokine production by Spred2−/− resident macrophages in vitro, and decreased CLP-induced leukocyte infiltration in vivo. Spred2−/− resident macrophages, but not neutrophils or elicited macrophages, exhibited increased phagocytic activity. Interestingly, surface expression of complement receptor 1/2 (CR1/2) was increased in Spred2−/− resident macrophages in response to lipopolysaccharide in a manner dependent on the ERK/MAPK pathway, and blocking CR1/2 in vivo resulted in reduced leukocyte infiltration and increased bacterial loads after CLP. Taken together, our results indicate that Spred2-deficiency protects mice from PMS via increased activation of the ERK/MAPK pathway and subsequent increase in innate immune responses. Thus, inhibiting Spred2 may present a novel means to prevent the development of PMS.

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“…These receptors are present on the major antigen-presenting cells in the GC, the FDC, and on GC B cells. It was shown previously that GCs will form normally in mice lacking CR1 and CR2, but collapse prematurely, before GCs can perform their important functions ( 120 ). This phenotype is strikingly similar to that seen in wild-type mice infected with B. burgdorferi .…”

Section: Interference Of B Burgdorferi With the Imentioning

confidence: 99%

Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts

Tracy

Baumgarth

2017

Front. Immunol.

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Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and other incidental hosts can develop Lyme disease, a serious inflammatory syndrome characterized by tissue inflammation of joints, heart, muscles, skin, and CNS. Although B. burgdorferi infection induces both innate and adaptive immune responses, they are ultimately ineffective in clearing the infection from reservoir hosts, leading to bacterial persistence. Here, we review some mechanisms by which B. burgdorferi evades the immune system of the rodent host, focusing in particular on the effects of innate immune mechanisms and recent findings suggesting that T-dependent B cell responses are subverted during infection. A better understanding of the mechanisms causing persistence in rodents may help to increase our understanding of the pathogenesis of Lyme disease and ultimately aid in the development of therapies that support effective clearance of the bacterial infection by the host’s immune system.

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Murine complement receptor 1 is required for germinal center B cell maintenance but not initiation

Cited by 5 publications

References 32 publications

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance

Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts

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