Human marginal-zone B cells

Spencer, Jo; Perry, M. E.; Dunn-Walters, Deborah K.

doi:10.1016/s0167-5699(98)01308-5

Cited by 374 publications

(105 citation statements)

References 48 publications

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“…It could alternatively occur in isolated B lymphoid follicles along the gut, as has been described for other species (see below). A [40] [41] similar pre-activated stage has been described for NK T cells , and, similarly to them, pre-activation of marginal zone B cells could be [42] driven by self or bacterial commensal antigens. For both these cellular populations, NKT and marginal zone B cells which are intermediate between the innate and adaptive immune system, this pre-activated stage may explain why they react very rapidly upon challenge by external bacterial antigens .…”

Section: Paradoxmentioning

confidence: 89%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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Infection with encapsulated bacteria can be prevented by vaccination with capsular polysaccharides, either plain or conjugated to a protein carrier. But results concerning these vaccinations raise several paradoxes. Polysaccharides from encapsulated bacteria are generally considered to be Tindependent antigens unable to trigger a T-dependent germinal center reaction, but strikingly, anti-polysaccharide antibodies are often mutated in humans. Polysaccharide-protein conjugate vaccines are able to induce a true T-dependent memory response with a rise in antibody titers and a switch to high affinity-IgG antibodies in children below 2 years of age, but neither the plain nor the conjugate vaccine can induce memory in older infants and adults. We propose some explanations to these paradoxes based on our recent observation that humans display a circulating splenic marginal zone B cell population with a pre-diversified immunoglobulin repertoire in charge of the immune response to T-independent vaccines. The impact of diseases generated by encapsulated bacteria has been underlined in many contexts and it is estimated that they are responsible for millions of children s deaths each year . Nevertheless, when looking at the abundant literature on immune responses to ' [1] encapsulated bacteria after vaccination by either plain or conjugated capsular polysaccharide vaccines, some paradoxes emerge which we would like to discuss. MESH Keywords Paradox 1It is generally accepted that bacterial capsular polysaccharides (CPS) are TI antigens that trigger specific B cells residing in the splenic marginal zone to secrete antibodies with opsonophagocytic properties against these bacteria . In rodents in which these responses have [2] been mostly studied, immunization do not induce an extensive proliferation within B cell follicles, neither the formation of germinal centers, and are for most of them taken care by unmutated germline antibodies . In humans on the contrary, the splenic marginal zone [3][4][5] contains B cells with mutated Ig receptors and mutated antibodies are raised in responses to encapsulated bacteria, these mutations [6][7][8] being responsible for the antibodies avidity for the immunizing antigen , . In all species, these TI responses do not trigger any [9 10] memory, the B cells engaged being able very rapidly to switch isotype and to secrete large amount of antibodies. These plasma cells can remain in the organism for various lengths of time, after which the response wanes out , . To account for the presence in humans of [11 12] mutated antibodies during a T-independent immune response that cannot normally trigger a cognate T-B dependent germinal center reaction, the classical explanation put forward by authors is that such responses are in fact taken care by memory B cells that bona fide have been primed by a previous encounter with the pathogen, either during an infection or by silent carriage . These memory B [13][14][15] cells would then eventually reside in the splenic marginal zone where they ...

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Section: Paradoxmentioning

confidence: 89%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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“…This suggests that CD1 ϩ B cells are prone to anti-self responses if inappropriate T cell help is provided. CD1 ϩ B cells are located in the marginal zones of lymphoid tissue, where B cells are more responsive to nonpeptide Ags (55)(56)(57), further suggesting that CD1 ϩ B cells are involved in Ab responses to nonpeptide Ags. Although this mechanism of Ag presentation may facilitate T and B cell interaction in host defense against microbial pathogens, our data suggest that CD1 Ag presentation may contribute to the pathogenesis of autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

115

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To understand the mechanism of T cell help for IgG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because 1) DN T cells are present at unusually high frequency in patients with SLE and can induce pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1+ APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-γ, whereas DN T cells from healthy donors produced IFN-γ, but no IL-4. In general, cells from patients with highly active disease produced high levels of IFN-γ; cells from those with little activity produced high IL-4. Coculture of CD1c-directly reactive T cells from healthy donors with CD1c+ B cells elicited IgM Abs, but little or no IgG. In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c+ B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of DN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c+ B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.

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“…In addition to mature follicular B cells, the other mature B lymphocytes that reside mainly in the spleen are the marginal zone B cells 3,5 .…”

Section: Bcl10 Absence Impairs Marginal Zone and B1 B Cell Developmentmentioning

confidence: 99%

“…The recirculating B2 B cells, also called follicular B cells, localize to the B lymphoid follicles of the spleen and lymph node 4 . The mostly nonrecirculating marginal zone B cells reside mainly around the periphery of the splenic lymphoid nodules 3,5 . The nonrecirculating B1 B cells are enriched in the peritoneal and pleural cavities 6 .…”

mentioning

confidence: 99%