Expression of Immunoglobulin Receptors with Distinctive Features Indicating Antigen Selection by Marginal Zone B Cells from Human Spleen

Colombo, Monica; Cutrona, Giovanna; Reverberi, Daniele; Bruno, Silvia; Ghiotto, Fabio; Tenca, Claudya; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Ceccarelli, Jenny; Salvi, Sandra; Boccardo, Simona; Calevo, Maria Grazia; Santanna, Amleto De; Truini, Mauro; Fais, Franco; Ferrarini, Manlio

doi:10.2119/molmed.2013.00069

Cited by 16 publications

(24 citation statements)

References 51 publications

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“…In addition, they found that most of the MZ-B cells were mutated, albeit with a lower average number of mutations than both GCs and class-switched B cells. However, the average number of mutations in human MZ-B cells (11.8) 67 is higher for both rat IgM + MZ-B cells (8.8) and rat IgG + MZ-B cells (7). 70 This might be because humans have fewer functional IGHV genes than rats.…”

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 93%

“…These findings contrasted markedly with findings in humans, where > 95% of the splenic MZ-B cells are mutated. 56,57,67 Two possible explanations for this difference are that only one particular IGHV gene family (viz., the IGHV5 family, the homologue of PC7183 in the mouse) has been analyzed in the (PVG) rat and that this IGHV gene family is not representative for other IGHV genes, or IGHV gene families. By establishing the genomic germline IGHV gene repertoire of the BN rat 68 as illustrated in Fig.…”

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

“…In humans, nearly all MZ-B cells are mutated. 56,57,67 The variation in frequency of mutated IGHV genes between the different IGHV families in rats may also contribute to the difference in mutated MZ-B cells between humans and rats because in humans the analysis of mutated IGHV genes has been restricted to a restrictive set of IGHV genes. Dunn-Walters et al 56 analyzed only two particular IGHV genes: the IGHV6 gene and IGHV4.21 gene.…”

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

“…They also showed that the high frequency of mutations is not only due to individual IGHV genes. Furthermore, Colombo et al 67 investigated and compared the presence of mutations in human IGHV1, IGHV3, and IGHV4 gene families among spleen-derived MZ-B cells (IgM high CD27 + ), GC B cells, and class switched B cells. In addition, they found that most of the MZ-B cells were mutated, albeit with a lower average number of mutations than both GCs and class-switched B cells.…”

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

“…However, whether mutated (memory) IgM + MZ-B cells are derived from GCs or whether they represent a GC-independent B cell population remains controversial. In humans, Colombo et al 67 also observed a small number of clonally related sequences that were shared between MZ-B cells and GC B cells, which indicates that mutated IgM + MZ-B cells can be derived from GCs. In contrast, Weill et al 11 and Weller et al 71 suggested that the (mutated) IgM + MZ-B cells are not GC-derived memory B cells.…”

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

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Heterogeneity of Memory Marginal Zone B Cells

2018

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The marginal zone (MZ) is largely composed of a unique subpopulation of B cells, the so-called MZ-B cells. At a molecular level, memory B cells are characterized by the presence of somatically mutated IGV genes. The earliest studies in the rat have documented the presence of hapten-specific MZ-B cells after immunization in the MZ. This work later received experimental support demonstrating that the IGHV-Cµ transcripts expressed by phenotypically defined splenic MZ-B cells (defined as CD90negIgMhighIgDlow B cells) can carry somatic hypermutation. However, only a minor fraction (< 10%–20%) of these MZ-B cells is mutated and is considered to represent memory B cells. Memory B cells can either be class-switched (IgG, IgA, IgE), or non–class-switched (IgM) B cells. B cells in the MZ are a heterogeneous population of cells and both naïve MZ-B cells; class switched and unswitched memory MZ-B cells are present at this unique site in the spleen. Naïve MZ-B cells carry unmutated Ig genes, produce low-affinity IgM molecules and constitute a first line of defense against invading pathogens. Memory MZ-B cells express high-affinity Ig molecules, directed to (microbial) antigens that have been encountered. In this review, we report on the memory compartment of splenic MZ-B cells in the rat to provide insights into the origin and function of these memory MZ-B cells.

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Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 93%

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

Section: Igm Expressing Marginal Zone Memory B Cellsmentioning

confidence: 99%

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Heterogeneity of Memory Marginal Zone B Cells

2018

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Disease‐biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations

Xochelli

Bikos

Polychronidou

et al. 2019

The Journal of Pathology

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The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross‐entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ‐related or not; n = 65 837) revealed four major clusters of cases sharing homologous (‘public’) heavy variable complementarity‐determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non‐malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen‐triggered, immune‐mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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