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B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
B cell differentiation within GC is highly regulated and compartmentalized (Figures 5–16and 2–20). B cells undergo exuberant proliferation in the follicle dark zone. The dividing centroblasts give rise to centrocytes which migrate to the basal light zone. Somatic mutation occurs during cell division and selection of centrocytes then takes place. If they are able to interact with antigen they migrate to the apical light zone. If not, they die and are engulfed by macrophages. Two signals are important for preventing the death of B cells in germinal centers: one is the cross-linking of Ig receptors by antigen complexed on FDC; the other is the interaction of B cell CD40 with its ligand (CD40L) on a T cell. Three possible fates are hypothesized for B cells surviving to enter the apical light zone: terminal differentiation to plasma cells; terminal differentiation to memory cells; or reentry to the dark zone to undergo further division and mutation.
The Lymphoid System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
When examining a lymphoid follicle, it is possible to clearly identify the light zone comprised of large, light-staining centrocytes and FDCs, the dark zone comprised of darkly stained centroblasts, and the surrounding mantle zone comprised of small, dark B-cells. The Ig variable genes of centroblasts diversify by somatic hypermutation, exit the cell cycle, and reexpress B-cell receptors as they become centrocytes located in the light zone. Centrocytes are then subject to selection based on the ability to bind antigens presented by FDC. Centrocytes with low-level affinity pass back into the dark zone and undergo apoptosis, whereas higher affinity cells survive in the germinal center and differentiate and proliferate into antibody-forming cells and memory B-cells. The apoptosis of lymphocytes that results in a starry sky appearance occurs most frequently in the dark zone of the follicle, but as demand increases for antibody production, greater cell turnover accompanied by tingible-bodied macrophages in the pale germinal center becomes apparent. B-cell maturation and differentiation result in the formation of early stage plasma cells, which translocate to the medullary cords where after further maturation produce and release antibodies.
Cutaneous Infiltrates: Lymphoid and Leukemic
Published in Omar P. Sangueza, Sara Moradi Tuchayi, Parisa Mansoori, Saleha A. Aldawsari, Amir Al-Dabagh, Amany A. Fathaddin, Steven R. Feldman, Dermatopathology Primer of Cutaneous Tumors, 2015
Other features: They contain a mixed population of cells: small lymphocytes, centrocyte-like cells, monocytoid B-cells, lymphoplasmacytoid cells and plasma cellsFollicular lymphoma may show follicular, follicular and diffuse, or diffuse patterns. Follicles are often variable in size and may fuse together. The follicle centers contain varying proportions of large and small centrocytes with cleaved nuclei and centroblasts with noncleaved nuclei and prominent nucleoli. Tangible body macrophages are absentDLBCL shows a diffuse infiltrate in the dermis and subcutis of large lymphocytes with features of centroblasts and immuno-blasts, mitotic figures are commonOther types of DLBCL in the skin are intravascular large B-cell lymphoma, plasmablastic lymphoma, DLBCL leg type
Biomarkers of lymphoma in Sjögren’s syndrome: what’s the latest?
Published in Expert Review of Clinical Immunology, 2022
Ioanna E. Stergiou, Athanasios-Dimitrios Bakasis, Stavroula Giannouli, Michael Voulgarelis
LESA is the histological hallmark of pSS. It is characterized by the presence of lymphocytes surrounding and infiltrating the salivary ducts, as well as by a disorganized and hyperplastic ductal epithelium [8]. The histopathologic features of LESA range from a fully benign lymphoid infiltrate, without B-cell Ig light chain restriction, to lesions of lymphoproliferation with centrocyte-like cells that often display Ig light chain restriction [82]. Christodoulou et al. demonstrated that the distribution of infiltrating mononuclear cells at the pSS SG lesions varies according to lesion severity, with CD4 + T-cells predominating in less severe lesions and B-cells in more severe ones. The type of the predominant lymphocytes, either T or B-cell, also correlates with disease manifestations, with patients presenting with B-cell predominance manifesting a more systemic disease phenotype [13]. To this end, research aimed to investigate the use of histological biomarkers as possible predictors for lymphoma development in the setting of pSS. As further analyzed below, focus score (FS) and the presence of ectopic germinal centers (GCs) are the histopathologic features more extensively studied for their possible correlation with pSS-related lymphoma development. We should though highlight, as presented by the study of Fisher et al. [83], that the histopathological evaluation of these features needs to be standardized when assessed in clinical trials in order to have more subjective calculations and avoid possible discrepancies in the reported results.
Tazemetostat: a treatment option for relapsed/refractory follicular lymphoma
Published in Expert Opinion on Pharmacotherapy, 2022
Patrizia Mondello, Stephen M Ansell
As EZH2 controls antigen presentation programs [31], its dysregulated function may also impact tumor-immune interactions. Reduced levels of MHC class I and II and decreased T cell infiltrates were observed in primary human B cell lymphomas and in murine models with conditional expression of mutant EZH2, supporting a potential immune escape mechanism [35]. Accordingly, treatment with EZH2i restored expression in MHC [35] as well as CD58 [36], a costimulatory molecule critical for immune response, in EZH2 mutant cell lines. Hence, EZH2 mutation likely disrupts GC exit, in part by preventing induction of antigen presentation and selection molecules, with concordant decreased interaction between GC B cells and T follicular helper cells. As this interaction is critical for GC proliferation and survival, its absence drives expansion of GC centrocytes that instead become dependent on follicular dendritic cells [37].
How can we assess and measure prognosis for MALT lymphoma? A review of current findings and strategies
Published in Expert Review of Hematology, 2021
Barbara Kiesewetter, Markus Raderer
Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) accounts for 8% of newly diagnosed non-Hodgkin lymphomas [1,2]. The postulated cell of origin is a post-germinal center marginal zone B-cell and corresponding infiltrates present with a pleiotropic pattern of lymphoma cells resembling typical centrocyte-like cells, plasma cells, small lymphocytes and monocytic B-cells intermingled with single blastoid cells, located around secondary lymph follicles [3]. According to the most recent WHO classification the corresponding basic immunophenotype is defined as CD20+ CD5-CD10-cyclinD1 – [2]. Clinically, the disease is characterized by (often multifocal) extranodal manifestations in acquired mucosa-associated tissues. Gastric involvement constitutes the most prominent primary site, but basically every organ can be affected including the ocular adnexa, the lungs, the parotid glands or the thyroid [1]. Median age at diagnosis is 65 years and females are slightly more often diagnosed with MALT lymphoma than males. Most patients present with an excellent performance status. In terms of pathogenesis, a causal association between chronic inflammatory processes and development of MALT lymphoma has been confirmed, exemplified by Helicobacter (H.) pylori-associated gastritis and gastric MALT lymphoma development [4–6].