Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

Weller, Sandra; Braun, M; Tan, Bruce K.; Rosenwald, Andreas; Cordier, Corinne; Conley, Mary Ellen; Plebani, Alessandro; Kumararatne, D S; Bonnet, Damien; Tournilhac, Olivier; Tchernia, Gil; Steiniger, Birte; Staudt, Louis M.; Casanova, Jean‐Laurent; Reynaud, Caroline; Weill, Jean Claude

doi:10.1182/blood-2004-01-0346

Cited by 710 publications

(860 citation statements)

References 35 publications

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“…A similar conclusion was reached by R. Carsetti and her colleagues in a recent [33] report, based on their study on the responding capacity asplenic or splenectomized patients to T-independent pneumococcal antigens .…”

Section: Paradoxsupporting

confidence: 76%

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: Paradoxsupporting

confidence: 76%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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“…The origin and role of IgDϩ memory B cells are still debated, but a study by Weller et al (18) suggested that this memory B cell subpopulation reflects a peri- (18). Additional support for this idea comes from studies which show that these cells are strongly diminished in splenectomized and in congenital asplenic patients, in whom class-switched memory B cells are present at normal frequency (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…Class-switched memory B cells undergo the maturation process in classic germinal centers (GCs) in secondary lymphoid organs (17). Little is known about the origin of IgDϩ memory B cells (IgDϩCD27ϩ), which are thought to be related to splenic marginal-zone B cells since they have similar phenotypic markers with different requirements for Ig receptor mutation (18).…”

mentioning

confidence: 99%

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Muhammad¹,

Roll²,

Einsele³

et al. 2009

Arthritis & Rheumatism

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“…Phenotypically, IgM þ memory B cells resemble marginal zone B cells and are thought to be their circulating counterparts. 19 Tsuiji et al 20 reported IgM þ memory B cells more frequently express VH3 family genes than do naive B cells. Noppe et al 21 reported VH usage in nodal follicular lymphoma cases as VH3 70%, VH4 19% and VH1 11%; Bahler et al 22 reported it as VH3 67%, VH4 22% and VH1 8%.…”

Section: Duodenal Follicular Lymphomamentioning

confidence: 99%

Duodenal and nodal follicular lymphomas are distinct: the former lacks activation-induced cytidine deaminase and follicular dendritic cells despite ongoing somatic hypermutations

et al. 2009

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Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activationinduced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (Po0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.

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Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

Cited by 710 publications

References 35 publications

Vaccination against encapsulated bacteria in humans: paradoxes

Vaccination against encapsulated bacteria in humans: paradoxes

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Duodenal and nodal follicular lymphomas are distinct: the former lacks activation-induced cytidine deaminase and follicular dendritic cells despite ongoing somatic hypermutations

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