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Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

Garraud O, Borhis G, Badr G, Degrelle S, Pozzetto B, Cognasse F, Richard Y - BMC Immunol. (2012)

Bottom Line: As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating.As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity.Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

View Article: PubMed Central - HTML - PubMed

Affiliation: EA3064-GIMAP, Université de Lyon, Saint-Etienne, France. olivier.garraud@efs.sante.fr

ABSTRACT
The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40(+) antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

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Organisation of the follicular and MZ B-cell compartments in the human spleen. (A) Schematic representation of the various T- and B-cell areas in the human spleen. PALS: periarteriolar lymphatic sheath (T-cell zone). (B) Staining of paraffin-embedded sections of human spleen with CD20 mAb revealed B-cell follicles (BZ) and a ring of B-cells separating the T-cell zone (TZ) from the red pulp (RP) (original magnification x10). (C) Sections of human spleen were simultaneously stained with PAX5, CD3 and ASM (alpha smooth muscle actin) mAbs. The network of fibroblast-like cells stained with the anti-ASM mAb (blue) subdivides the outer (OMZ) from the inner marginal zone around B-cell follicles (PAX5+, green) and separates the T-cell zone (CD3+, red) from the RP (left panels) (original magnification x10). In the upper left panel, a germinal centre (GC) is visible within the B-cell follicle. General tissue organisation is shown by DAPI staining of nuclei (right panels).
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Figure 1: Organisation of the follicular and MZ B-cell compartments in the human spleen. (A) Schematic representation of the various T- and B-cell areas in the human spleen. PALS: periarteriolar lymphatic sheath (T-cell zone). (B) Staining of paraffin-embedded sections of human spleen with CD20 mAb revealed B-cell follicles (BZ) and a ring of B-cells separating the T-cell zone (TZ) from the red pulp (RP) (original magnification x10). (C) Sections of human spleen were simultaneously stained with PAX5, CD3 and ASM (alpha smooth muscle actin) mAbs. The network of fibroblast-like cells stained with the anti-ASM mAb (blue) subdivides the outer (OMZ) from the inner marginal zone around B-cell follicles (PAX5+, green) and separates the T-cell zone (CD3+, red) from the RP (left panels) (original magnification x10). In the upper left panel, a germinal centre (GC) is visible within the B-cell follicle. General tissue organisation is shown by DAPI staining of nuclei (right panels).

Mentions: In contrast to the mouse, the human spleen lacks a marginal sinus, and MZ surrounds B-cell follicles but not the PALS (Periarteriolar Lymphatic Sheath or T-cell rich area). However, the perifollicular zone is an intermediate area between the MZ and the red pulp (Figure 1). This zone presents strong similarities to the red pulp because of terminal sinuses, blood-filled spaces, sheathed capillaries without endothelial lining, and scattered B- and T-cells. Because terminal vessels directly open into the perifollicular zone, Ags and leukocytes likely exit the circulation in this structure and traffic either to the MZ or to the red pulp[42,43]. A meshwork of fibroblast-like cells expressing Alpha Smooth Muscle actin (ASM) and MadCAM-1 (Mucosal addressing cell adhesion molecule 1) subdivides the MZ into a large inner and a small outer compartment, the latter being in close contact with the perifollicular zone. Along the network of ASM-positive cells, a small ring of B-cells delimits the T-cell zone from the red pulp, whereas a ring of T-cells is frequently present between the inner and outer MZ[44]. The MZM and MMM subsets that respectively populate the outer and inner MZ in mice are lacking in humans. However, human macrophages expressing CD68 (lysosome/macrosialin) and CD169 preferentially form sheaths around capillaries in the perifollicular area, and they can also be present as scattered cells expressing DC-SIGN[45,46]. Whether these macrophages may replace MZM in trapping pathogens and interacting with MZ B-cells remains to be established. In humans, CD11c+ CD205+ DCs are also intertwined with MadCAM1+ cells at the inner border of the perifollicular zone, whereas BDCA-2+ plasmacytoid DCs are present in the MZ and T-cell zones under steady-state conditions[47-50].


Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

Garraud O, Borhis G, Badr G, Degrelle S, Pozzetto B, Cognasse F, Richard Y - BMC Immunol. (2012)

Organisation of the follicular and MZ B-cell compartments in the human spleen. (A) Schematic representation of the various T- and B-cell areas in the human spleen. PALS: periarteriolar lymphatic sheath (T-cell zone). (B) Staining of paraffin-embedded sections of human spleen with CD20 mAb revealed B-cell follicles (BZ) and a ring of B-cells separating the T-cell zone (TZ) from the red pulp (RP) (original magnification x10). (C) Sections of human spleen were simultaneously stained with PAX5, CD3 and ASM (alpha smooth muscle actin) mAbs. The network of fibroblast-like cells stained with the anti-ASM mAb (blue) subdivides the outer (OMZ) from the inner marginal zone around B-cell follicles (PAX5+, green) and separates the T-cell zone (CD3+, red) from the RP (left panels) (original magnification x10). In the upper left panel, a germinal centre (GC) is visible within the B-cell follicle. General tissue organisation is shown by DAPI staining of nuclei (right panels).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526508&req=5

Figure 1: Organisation of the follicular and MZ B-cell compartments in the human spleen. (A) Schematic representation of the various T- and B-cell areas in the human spleen. PALS: periarteriolar lymphatic sheath (T-cell zone). (B) Staining of paraffin-embedded sections of human spleen with CD20 mAb revealed B-cell follicles (BZ) and a ring of B-cells separating the T-cell zone (TZ) from the red pulp (RP) (original magnification x10). (C) Sections of human spleen were simultaneously stained with PAX5, CD3 and ASM (alpha smooth muscle actin) mAbs. The network of fibroblast-like cells stained with the anti-ASM mAb (blue) subdivides the outer (OMZ) from the inner marginal zone around B-cell follicles (PAX5+, green) and separates the T-cell zone (CD3+, red) from the RP (left panels) (original magnification x10). In the upper left panel, a germinal centre (GC) is visible within the B-cell follicle. General tissue organisation is shown by DAPI staining of nuclei (right panels).
Mentions: In contrast to the mouse, the human spleen lacks a marginal sinus, and MZ surrounds B-cell follicles but not the PALS (Periarteriolar Lymphatic Sheath or T-cell rich area). However, the perifollicular zone is an intermediate area between the MZ and the red pulp (Figure 1). This zone presents strong similarities to the red pulp because of terminal sinuses, blood-filled spaces, sheathed capillaries without endothelial lining, and scattered B- and T-cells. Because terminal vessels directly open into the perifollicular zone, Ags and leukocytes likely exit the circulation in this structure and traffic either to the MZ or to the red pulp[42,43]. A meshwork of fibroblast-like cells expressing Alpha Smooth Muscle actin (ASM) and MadCAM-1 (Mucosal addressing cell adhesion molecule 1) subdivides the MZ into a large inner and a small outer compartment, the latter being in close contact with the perifollicular zone. Along the network of ASM-positive cells, a small ring of B-cells delimits the T-cell zone from the red pulp, whereas a ring of T-cells is frequently present between the inner and outer MZ[44]. The MZM and MMM subsets that respectively populate the outer and inner MZ in mice are lacking in humans. However, human macrophages expressing CD68 (lysosome/macrosialin) and CD169 preferentially form sheaths around capillaries in the perifollicular area, and they can also be present as scattered cells expressing DC-SIGN[45,46]. Whether these macrophages may replace MZM in trapping pathogens and interacting with MZ B-cells remains to be established. In humans, CD11c+ CD205+ DCs are also intertwined with MadCAM1+ cells at the inner border of the perifollicular zone, whereas BDCA-2+ plasmacytoid DCs are present in the MZ and T-cell zones under steady-state conditions[47-50].

Bottom Line: As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating.As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity.Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

View Article: PubMed Central - HTML - PubMed

Affiliation: EA3064-GIMAP, Université de Lyon, Saint-Etienne, France. olivier.garraud@efs.sante.fr

ABSTRACT
The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40(+) antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

Show MeSH
Related in: MedlinePlus