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Subversion of the B-cell compartment during parasitic, bacterial, and viral infections.

Borhis G, Richard Y - BMC Immunol. (2015)

Bottom Line: Recent studies on HIV infection have identified new human B-cell subsets with a potentially important impact on anti-viral immunity.Current work highlights the occurrence of similar B-cell alterations in other viral, bacterial, and parasitic infections, suggesting that common strategies have been developed by pathogens to counteract protective immunity.For this review, we have selected key examples of human infections for which B-cell alterations have been described, to highlight the similarities and differences in the immune responses to a variety of pathogens.

View Article: PubMed Central - PubMed

Affiliation: INSERM u1016, Cochin Institute, Department of Infection, Immunity and Inflammation, 27 rue du Faubourg St-Jacques, Roussy Bldg., Paris, 75014, France. gwenoline.borhis@inserm.fr.

ABSTRACT
Recent studies on HIV infection have identified new human B-cell subsets with a potentially important impact on anti-viral immunity. Current work highlights the occurrence of similar B-cell alterations in other viral, bacterial, and parasitic infections, suggesting that common strategies have been developed by pathogens to counteract protective immunity. For this review, we have selected key examples of human infections for which B-cell alterations have been described, to highlight the similarities and differences in the immune responses to a variety of pathogens. We believe that further comparisons between these models will lead to critical progress in the understanding of B-cell mechanisms and will open new target avenues for therapeutic interventions.

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Related in: MedlinePlus

Differentiation and trafficking of innate and follicular B-cells. Mouse, and probably human, B-1 cells home to the serous cavities in steady state conditions and migrate to the spleen after activation by pathogens where they differentiate into natural Immunoglobulin (Ig) M-producing cells. Follicular (FO) B-cells are produced from bone marrow precursors that mature sequentially into pro-B and pre-B cells (not detailed) and immature mIgM+ B-cells. Immature-transitional 1 (Trans 1) B-cells migrate through the blood into spleen marginal zone (MZ) where they mature into transitional 2 (Trans 2) B-cells. Based on the balance between BCR-Notch2 signals, they next differentiate into FO or MZ B-cells. MZ B cells secrete low affinity IgM after antigenic stimulation. In the germinal center (GC), FO helper T-cells (TFH) support the selection and survival of B-cell clones with high-affinity BCR. Once selected, these clones differentiate into two types of effector cells, memory B-cells (Mem B) and plasma cell precursors (plasmablasts, PBl), and leave the spleen. The PBl migrate into the bone marrow and constitute a pool of long-lived plasma cells producing high-affinity Ig, whereas the Mem B migrate into extra-follicular areas in secondary lymphoid tissues.
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Fig1: Differentiation and trafficking of innate and follicular B-cells. Mouse, and probably human, B-1 cells home to the serous cavities in steady state conditions and migrate to the spleen after activation by pathogens where they differentiate into natural Immunoglobulin (Ig) M-producing cells. Follicular (FO) B-cells are produced from bone marrow precursors that mature sequentially into pro-B and pre-B cells (not detailed) and immature mIgM+ B-cells. Immature-transitional 1 (Trans 1) B-cells migrate through the blood into spleen marginal zone (MZ) where they mature into transitional 2 (Trans 2) B-cells. Based on the balance between BCR-Notch2 signals, they next differentiate into FO or MZ B-cells. MZ B cells secrete low affinity IgM after antigenic stimulation. In the germinal center (GC), FO helper T-cells (TFH) support the selection and survival of B-cell clones with high-affinity BCR. Once selected, these clones differentiate into two types of effector cells, memory B-cells (Mem B) and plasma cell precursors (plasmablasts, PBl), and leave the spleen. The PBl migrate into the bone marrow and constitute a pool of long-lived plasma cells producing high-affinity Ig, whereas the Mem B migrate into extra-follicular areas in secondary lymphoid tissues.

Mentions: The TD Ab response relies on the production of two kinds of effectors from FO naïve (IgDhiIgM+CD27−CD21int) B-cells: memory B-cells (MemB) and long-lived PC, who produce high-affinity Abs (Figure 1). This response occurs in lymphoid tissues, where naïve B-cells are organized in follicles in close contact with T-cell zones. Once activated by TD antigens (mainly proteins), naïve B-cells rapidly proliferate at the T/B border and generate PC that locally produce low-affinity IgM within a few days [16]. Concomitantly activated B-cells produce germinal center (GC) founder cells, which proliferate in the center of follicles. These proliferating cells no longer express BCR and become CD27int and Bcl6+. After a set number of cell cycles, they become non-proliferating centrocytes expressing membrane switched and hyper-mutated BCR. Subsequent interactions of these centrocytes with a specialized T-cell subset, FO helper T-cells (TFH), and with Ag on FO dendritic cells (DC) determine the selection and survival of high-affinity B-cell clones [17-19]. Through cognate interactions and TFH-produced cytokines (mostly IL21, but also IL4 and IL10), selected B-cell clones differentiate into MemB and PC precursors. After their trafficking into bone marrow, PC precursors constitute a pool of long-lived PC producing high-affinity Abs whereas MemB reside in extra-follicular areas in lymphoid tissues until further encounter with similar Ags. Thus, the TD response is a fine-tuned, multistep process, which constitutes an ideal target for pathogen-induced subversion, as suggested by the altered MemB phenotypes observed during many infections, particularly chronic ones.Figure 1


Subversion of the B-cell compartment during parasitic, bacterial, and viral infections.

Borhis G, Richard Y - BMC Immunol. (2015)

Differentiation and trafficking of innate and follicular B-cells. Mouse, and probably human, B-1 cells home to the serous cavities in steady state conditions and migrate to the spleen after activation by pathogens where they differentiate into natural Immunoglobulin (Ig) M-producing cells. Follicular (FO) B-cells are produced from bone marrow precursors that mature sequentially into pro-B and pre-B cells (not detailed) and immature mIgM+ B-cells. Immature-transitional 1 (Trans 1) B-cells migrate through the blood into spleen marginal zone (MZ) where they mature into transitional 2 (Trans 2) B-cells. Based on the balance between BCR-Notch2 signals, they next differentiate into FO or MZ B-cells. MZ B cells secrete low affinity IgM after antigenic stimulation. In the germinal center (GC), FO helper T-cells (TFH) support the selection and survival of B-cell clones with high-affinity BCR. Once selected, these clones differentiate into two types of effector cells, memory B-cells (Mem B) and plasma cell precursors (plasmablasts, PBl), and leave the spleen. The PBl migrate into the bone marrow and constitute a pool of long-lived plasma cells producing high-affinity Ig, whereas the Mem B migrate into extra-follicular areas in secondary lymphoid tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374497&req=5

Fig1: Differentiation and trafficking of innate and follicular B-cells. Mouse, and probably human, B-1 cells home to the serous cavities in steady state conditions and migrate to the spleen after activation by pathogens where they differentiate into natural Immunoglobulin (Ig) M-producing cells. Follicular (FO) B-cells are produced from bone marrow precursors that mature sequentially into pro-B and pre-B cells (not detailed) and immature mIgM+ B-cells. Immature-transitional 1 (Trans 1) B-cells migrate through the blood into spleen marginal zone (MZ) where they mature into transitional 2 (Trans 2) B-cells. Based on the balance between BCR-Notch2 signals, they next differentiate into FO or MZ B-cells. MZ B cells secrete low affinity IgM after antigenic stimulation. In the germinal center (GC), FO helper T-cells (TFH) support the selection and survival of B-cell clones with high-affinity BCR. Once selected, these clones differentiate into two types of effector cells, memory B-cells (Mem B) and plasma cell precursors (plasmablasts, PBl), and leave the spleen. The PBl migrate into the bone marrow and constitute a pool of long-lived plasma cells producing high-affinity Ig, whereas the Mem B migrate into extra-follicular areas in secondary lymphoid tissues.
Mentions: The TD Ab response relies on the production of two kinds of effectors from FO naïve (IgDhiIgM+CD27−CD21int) B-cells: memory B-cells (MemB) and long-lived PC, who produce high-affinity Abs (Figure 1). This response occurs in lymphoid tissues, where naïve B-cells are organized in follicles in close contact with T-cell zones. Once activated by TD antigens (mainly proteins), naïve B-cells rapidly proliferate at the T/B border and generate PC that locally produce low-affinity IgM within a few days [16]. Concomitantly activated B-cells produce germinal center (GC) founder cells, which proliferate in the center of follicles. These proliferating cells no longer express BCR and become CD27int and Bcl6+. After a set number of cell cycles, they become non-proliferating centrocytes expressing membrane switched and hyper-mutated BCR. Subsequent interactions of these centrocytes with a specialized T-cell subset, FO helper T-cells (TFH), and with Ag on FO dendritic cells (DC) determine the selection and survival of high-affinity B-cell clones [17-19]. Through cognate interactions and TFH-produced cytokines (mostly IL21, but also IL4 and IL10), selected B-cell clones differentiate into MemB and PC precursors. After their trafficking into bone marrow, PC precursors constitute a pool of long-lived PC producing high-affinity Abs whereas MemB reside in extra-follicular areas in lymphoid tissues until further encounter with similar Ags. Thus, the TD response is a fine-tuned, multistep process, which constitutes an ideal target for pathogen-induced subversion, as suggested by the altered MemB phenotypes observed during many infections, particularly chronic ones.Figure 1

Bottom Line: Recent studies on HIV infection have identified new human B-cell subsets with a potentially important impact on anti-viral immunity.Current work highlights the occurrence of similar B-cell alterations in other viral, bacterial, and parasitic infections, suggesting that common strategies have been developed by pathogens to counteract protective immunity.For this review, we have selected key examples of human infections for which B-cell alterations have been described, to highlight the similarities and differences in the immune responses to a variety of pathogens.

View Article: PubMed Central - PubMed

Affiliation: INSERM u1016, Cochin Institute, Department of Infection, Immunity and Inflammation, 27 rue du Faubourg St-Jacques, Roussy Bldg., Paris, 75014, France. gwenoline.borhis@inserm.fr.

ABSTRACT
Recent studies on HIV infection have identified new human B-cell subsets with a potentially important impact on anti-viral immunity. Current work highlights the occurrence of similar B-cell alterations in other viral, bacterial, and parasitic infections, suggesting that common strategies have been developed by pathogens to counteract protective immunity. For this review, we have selected key examples of human infections for which B-cell alterations have been described, to highlight the similarities and differences in the immune responses to a variety of pathogens. We believe that further comparisons between these models will lead to critical progress in the understanding of B-cell mechanisms and will open new target avenues for therapeutic interventions.

Show MeSH
Related in: MedlinePlus