Human Immunoglobulin M Memory B Cells Controlling <i>Streptococcus pneumoniae</i> Infections Are Generated in the Spleen

Kruetzmann, Stephanie; Rosado, Maria Manuela; Weber, Holger; Germing, Ulrich; Tournilhac, Olivier; Peter, Hans; Berner, Reinhard; Peters, Anke; Boehm, Thomas; Plebani, Alessandro; Quinti, Isabella; Carsetti, Rita

doi:10.1084/jem.20022020

Cited by 582 publications

(577 citation statements)

References 18 publications

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“…It may, therefore, represent a watershed zone which is more vulnerable than other zones to a fall in splenic perfusion pressure. Around half of the B cells in the blood express the CD27 marker and are considered memory B cells [18,19]. There are two populations of memory B cells-switched memory B cells and IgM memory B cells.…”

Section: Discussionmentioning

confidence: 99%

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

Foley

Kavnoudias

Cameron

et al. 2015

Cardiovasc Intervent Radiol

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Purpose To compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels. Materials and Methods Patients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population. Results Of the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation-a difference that could not be attributed to differences in age, grade of injury or residual splenic volume. Conclusion IgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.

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Section: Discussionmentioning

confidence: 99%

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

Foley

Kavnoudias

Cameron

et al. 2015

Cardiovasc Intervent Radiol

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“…The reduction in the frequency of preswitch memory B cells was detected as early as week 12 and for the postswitch subset after 6 months. The relatively early reduction in preswitch memory B cells may reflect their turnover rate, since studies of splenectomized and congenital asplenic patients (34,35) indicate a shorter lifespan of preswitch than postswitch memory B cells (34). Preswitch memory B cells have been related to circulating marginal zone B cells.…”

Section: Discussionmentioning

confidence: 99%

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

Roll¹,

Muhammad²,

M³

et al. 2011

Arthritis & Rheumatism

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Objective. Interleukin-6 (IL-6) receptor inhibition by tocilizumab was recently licensed for the treatment of rheumatoid arthritis (RA). IL-6 induces in vitro differentiation of B cells into antibody-forming cells; however, the in vivo effects of IL-6 inhibition on the B cell compartment are currently not known. The purpose of this study was to examine this feature.Methods. Sixteen patients with active RA were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline, week 12, and week 24.Results. Memory B cell subsets declined significantly during tocilizumab therapy. Preswitch memory B cells decreased from a median of 19.6% to 12.3% at week 24 and postswitch memory B cells declined from a median of 18.6% to 15.0% at week 24 (P ‫؍‬ 0.04). In parallel, CD19؉IgA؉ and CD19؉IgG؉ B cells decreased significantly. The proportion of IgA-expressing B cells fell from a median of 9.2% at baseline to 4.3% at week 12 and to 3.6% at week 24 (P ‫؍‬ 0.01). IgG؉ B cells declined from a median of 6.7% at baseline to 4.9% at week 12 (P ‫؍‬ 0.007) and 2.8% at week 24 (P ‫؍‬ 0.01). In parallel, serum levels of IgA and IgG were significantly diminished at week 24 (P < 0.05). There was a good correlation between relative and absolute numbers of IgA؉ B cells with serum IgA at week 24.Conclusion. Tocilizumab induced a significant reduction in the frequency of peripheral preswitch and postswitch memory B cells. In addition, the number of IgG؉ and IgA؉ B cells declined and correlated well with reduced serum immunoglobulin levels. The data indicate that IL-6 blockade affects the B cell hyperreactivity in RA patients.

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“…It is also known that blood dendritic cells interact with marginal zone (MZ) B cells to initiate TI-2 immune responses as polysaccharide antigens localize preferentially to these (MZ) B cells found in spleen (Achtman et al 2009;Klouwenberg and Bont 2008). The splenic marginal zone (MZ) has been implicated as a source of circulating IgM memory B cells (Kreutzmann et al 2003). These findings reveal a larger role for polysaccharides in immune recognition than currently appreciated.…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

Majumder

Staats

Sarkar-Roy

et al. 2009

HUGO J

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Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed [2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid.

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Human Immunoglobulin M Memory B Cells Controlling Streptococcus pneumoniae Infections Are Generated in the Spleen

Cited by 582 publications

References 18 publications

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

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