Expression pattern analysis of BAFF, BAFF-R, TACI, BCMA, CXCL13 and CXCR5 in human tonsils
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1
Universidad de Guadalajara, Instituto de Investigación en Ciencias Biomédicas, Mexico
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2
Universidad de Guadalajara, Departamento de Microbiología y Patología, Mexico
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3
Universidad de Guadalajara, Departamento de Fisiología, Mexico
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4
Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Mexico
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5
Universidad de Guadalajara, Departamento de Neurociencias, Mexico
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6
Universidad de Guadalajara, Departamento de Fisiología, Mexico
INTRODUCTION: B-cell activating factor (BAFF; also known as B-lymphocyte stimulator [BLyS]) is a cytokine member of the tumor necrosis family (TNF) superfamily, existing either as a type 2 transmembrane protein or as a soluble form. BAFF contributes to B cell survival, maturation, activation and differentiation. BAFF can bind to three receptors: BAFF receptor (BAFF-R; also known as BLyS receptor 3 [BR-3]), B-cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI). BCMA and TACI also bind to another TNF family member, a proliferation-inducing ligand (APRIL), whereas BAFF-R is specific for BAFF. It is known that BAFF-R is essential for both survival and maturation of immature B cells, whereas TACI is critical for T-cell independent responses of B-cells, immunoglobulin (Ig) class-switch and is considered a negative regulator of B-cell homeostasis. BCMA promotes plasma cell survival. BAFF is expressed by monocytes, macrophages, neutrophils and dendritic cells.
B cells and activated T cells also are able to produce BAFF in secondary lymphoid tissues such as spleen, lymph nodes and tonsils. The structures known as germinal centers (GCs) are important for T-dependent antibody responses and these are the main sites for the generation of high affinity antibody-secreting plasma cells and memory B cells through the processes of clonal proliferation, somatic hypermutation and selection. Morphologically, two compartments are described inside the GCs: dark zone, where lymphocytes are closely packed; and the light zone, in which most is occupied by a follicular dendritic cells (FDC) network and follicular B cells.
A key molecule that mediates B and T cells recruitment into follicles is chemokine CXCL13 (also named B-cell attracting chemokine [BCA-1]) through its receptor CXCR5. CXCL13 is abundant in the light zone, where it accumulates due to its expression mainly by FDC. Previous studies have already described the expression of BAFF, CXCL13 and their receptors in secondary lymphatic tissues, such as tonsils, but not with an integrative point of view neither highlighting their role in the GC formation and regulation. The mechanisms of how they contribute together at different stages in the GC reaction remains unknown. It has been suggested that BAFF and CXCL13 synergize to promote the GCs formation and development, favoring migration dynamics of GCs cells.
OBJECTIVE: The aim of this study was to describe and compare the distinct expression profiles of BAFF, BAFF-R, TACI, BCMA, CXCL13 and CXCR5 in GCs.
METHODOLOGY: Human tonsil biopsies (n=8) were obtained from individuals subjected to a tonsillectomy, all of them under written informed consent. Tissues were paraffin embedded and the expression of molecules and their receptors was assessed by immunohistochemistry using rat, mouse and rabbit anti-human primary antibodies (Abcam, USA), ABC detection system and DAB as substrate. Immunostaining was evaluated by one experienced pathologist.
RESULTS: The GCs were identified by the expression of CD21 to assess the presence of FDC inside follicles. BAFF expression had an irregular distribution among lymphocyte infiltrate, but also it was clearly located within GC. BAFF-R was expressed with high intensity on cells from the mantle zone in an asymmetric way, and less intense in a few cells inside GC. TACI displayed an extended distribution on both GC and interfollicular areas, with a clear difference between cells around GC less stained than those within GC. BCMA distribution was very similar to TACI; moreover, some marked cells were observed in reticulated regions beside blood vessels. CXCL13 was located at interstitial spaces as well inside GC, however a higher marking density was seen towards light zone. CXCR5 expression by mononuclear cells showed a homogenous distribution; furthermore, many isolated interfollicular cells were strongly stained.
CONCLUSIONS: Our study exhibits an integral view of how these molecules are present in secondary lymphoid tissues and their contribution to GC formation. Nevertheless, further analyses are necessary in order to elucidate the immunophenotype of these cells and the link between their localization and their role in physiologic immune responses.
Keywords:
Germinal Center,
BAFF,
BAFF-R,
TACI,
BCMA,
CXCL13,
CXCR5
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Adaptive Immunity
Citation:
Carrillo-Ballesteros
FJ,
Palafox-Sánchez
CA,
Muñoz-Valle
JF,
Franco-Topete
R,
Govea-Camacho
LH,
Luquín
S,
Del Toro-Arreola
S and
Oregon-Romero
E
(2015). Expression pattern analysis of BAFF, BAFF-R, TACI, BCMA, CXCL13 and CXCR5 in human tonsils.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00044
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Received:
14 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
PhD. Edith Oregon-Romero, Universidad de Guadalajara, Instituto de Investigación en Ciencias Biomédicas, Guadalajara, Jalisco, Mexico, oregon_edith@hotmail.com