Heterogeneity of Memory Marginal Zone B Cells

Hendricks, Jacobus; Bos, Nicolaas A.; Kroese, Frans G. M.

doi:10.1615/critrevimmunol.2018024985

Cited by 28 publications

(21 citation statements)

References 79 publications

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“…Purified s-BCS enable more detailed BcR IG repertoire analyses than unfractionated B cells, especially for less represented populations that can escape characterization when unfractionated B cells are analyzed. Furthermore, the splenic tissue allows for the isolation of s-BCS that are normally not present in the blood circulation (GC B cells) or, when present (MZ B cells), represent only a small fraction of the subpopulation itself (Bagnara et al 2015;Seifert and Kuppers 2016;Hendricks et al 2018). The spleen provides evident advantages for normal, adult BcR IG repertoire analyses over other secondary lymphoid tissues, such as the tonsils, which are frequently removed at young age and in the case of chronic infection.…”

Section: Discussionmentioning

confidence: 99%

Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach

Colombo

Bagnara

Reverberi

et al. 2020

Mol Med

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Background: B cell receptor Immunoglobulin (BcR IG) repertoire of Chronic Lymphocytic Leukemia (CLL) is characterized by the expression of quasi-identical BcR IG. These are observed in approximately 30% of patients, defined as stereotyped receptors and subdivided into subsets based on specific VH CDR3 aa motifs and phylogenetically related IGHV genes. Although relevant to CLL ontogeny, the distribution of CLL-biased stereotyped immunoglobulin rearrangements (CBS-IG) in normal B cells has not been so far specifically addressed using modern sequencing technologies. Here, we have investigated the presence of CBS-IG in splenic B cell subpopulations (s-BCS) and in CD5 + and CD5 − B cells from the spleen and peripheral blood (PB). Methods: Fractionation of splenic B cells into 9 different B cell subsets and that of spleen and PB into CD5 + and CD5 − cells were carried out by FACS sorting. cDNA sequences of BcR IG gene rearrangements were obtained by NGS. Identification of amino acidic motifs typical of CLL stereotyped subsets was carried out on IGHV1-carrying gene sequences and statistical evaluation has been subsequently performed to assess stereotypes distribution. Results: CBS-IG represented the 0.26% average of IGHV1 genes expressing sequences, were detected in all of the BCS investigated. CBS-IG were more abundant in splenic and circulating CD5 + B (0.57%) cells compared to CD5 − B cells (0.17%). In all instances, most CBS IG did not exhibit somatic hypermutation similar to CLL stereotyped receptors. However, compared to CLL, they exhibited a different CLL subset distribution and a broader utilization of the genes of the IGHV1 family. Conclusions: CBS-IG receptors appear to represent a part of the "public" BcR repertoire in normal B cells. This repertoire is observed in all BCS excluding the hypothesis that CLL stereotyped BcR accumulate in a specific B cell subset, potentially capable of originating a leukemic clone. The different relative representation of CBS-IG in normal B cell subgroups suggests the requirement for additional selective processes before a full transformation into CLL is achieved.

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Section: Discussionmentioning

confidence: 99%

Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach

Colombo

Bagnara

Reverberi

et al. 2020

Mol Med

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“…This is especially interesting in light of evidence that MZB cells have high CD1d expression and have been shown to be required for normal IgG3 production (26). However, if MZB cells have the capacity to enter the GC reaction in this situation is still an unresolved question (27,28).…”

Section: Significancementioning

confidence: 99%

Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses

Sedimbi

Hägglöf

Garimella

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Invariant natural killer T (iNKT) cells serve as early rapid responders in the innate immune response to self-derived autoantigens and pathogen-derived danger signals and antigens. iNKT cells can serve both as helpers for effector B cells and negatively regulate autoreactive B cells. Specifically, iNKT cells drive B cell proliferation, class switch, and antibody production to induce primary antigen-specific immune responses. On the other hand, inflammasome-mediated activation drives accumulation of neutrophils, which license iNKT cells to negatively regulate autoreactive B cells via Fas ligand (FasL). This positions iNKT cells at an apex to support or inhibit B cell responses in inflammation. However, it is unknown which effector mechanism dominates in the face of cognate glycolipid activation during chronic inflammation, as might result from glycolipid vaccination or infection during chronic autoimmune disease. We stimulated iNKT cells by cognate glycolipid antigen α-galactosylceramide (αGalCer) and measured B cell activation during interleukin 18 (IL-18)-induced chronic inflammation. Moreover, glycolipid-activated iNKT cells increased the serum concentration of autoantibodies, frequency of germinal center (GC) B cells, and antigen-specific plasma cells induced during chronic IL-18–mediated inflammation, as compared with IL-18 alone. Further, activation of iNKT cells via cognate glycolipid during IL-18–mediated inflammation overrides the licensing function of neutrophils, instead inducing iNKT follicular helper (iNKTfh) cells that in turn promote autoimmunity. Thus, our data demonstrate that glycolipids which engage iNKT cells support antigen-specific B cell help during inflammasome-mediated inflammation.

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“…The pattern of surface molecule expression IgM high IgD low CD21 high CD23 low makes rodent splenic MZB cells easily distinguished from the naïve recirculating follicular B cells that are IgM low IgD high CD21 intermediate CD23 high . 10 The mouse MZB cells also express CD1d, a molecule involved in presenting lipid molecules to natural killer (NK) cells. 10,11 With B1 B cells that are located essentially in peritoneal and pleural cavities, MZB cells are suggested to be engaged in the innate arm of immune defence.…”

Section: Marginal Zone B Cellsmentioning

confidence: 99%

“…10 The mouse MZB cells also express CD1d, a molecule involved in presenting lipid molecules to natural killer (NK) cells. 10,11 With B1 B cells that are located essentially in peritoneal and pleural cavities, MZB cells are suggested to be engaged in the innate arm of immune defence. 1,5 Marginal zone B cells are considered to be 'innate B lymphocytes' on the basis of their activated phenotype that allows rapid proliferation and differentiation into IgM plasmablast cells when encountered with bloodborne, thymus-independent (TI) Ags.…”

Section: Marginal Zone B Cellsmentioning

confidence: 99%

“…9 A smaller proportion (about 20%) of MZB cells in rodents have a phenotype of memory cells with a mutated high affinity Ig molecules which is considered to be T cell-dependent process. 10 Thus, the MZ, which is composed of promptly responding naïve and memory MZB cells, is a great platform for innate-like and adaptive antibody responses to microbial antigens, both TI and TD antigens.…”

Section: Marginal Zone B Cellsmentioning

confidence: 99%

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Putative role of marginal zone B cells in pathophysiological processes

Marinković

Marinkovic²

2020

Scand J Immunol

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The maintenance of inner integrity of an organism is founded on the proper performance of two immunity branches, innate and adaptive immune responses. Recently, it became apparent that subset of splenic B cells named marginal zone B cells (MZB cells) exhibits unique developmental and functional features that bridge these two immunity branches. Strategically positioned at the site where blood and lymph are filtered, MZB cells represent a population of sentinels that rapidly proliferate and differentiate into IgM plasmablast cells when encountered with blood‐borne, thymus‐independent (TI) Ags. Moreover, MZB cells have intrinsic capability to induce potent CD4+ helper T cell response and cytokine production upon stimulation with soluble antigens. Due to their ability to overcome a time gap prior the establishment of the full adaptive response towards pathogens, MZB cells connect and direct innate and adaptive immunity. An additional interesting characteristic of MZB cells is capacity to function as regulatory cells in autoimmune processes. MZB cells may also contribute to the control of autoimmunity via the induction of tolerance by apoptotic cells. Importantly, in the clear association with inflammation and autoimmunity, MZB cells may transform into MALT lymphoma, representing a concurrence point for the infection, immunity and malignancy. This paper presents an insight into the complex biology of marginal zone B cells and their role in intertwining and directing innate and adaptive immune processes at the physiological and pathological level.

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Heterogeneity of Memory Marginal Zone B Cells

Cited by 28 publications

References 79 publications

Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach

Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach

Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses

Putative role of marginal zone B cells in pathophysiological processes

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