Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions

Seifert, Marc; Przekopowitz, Martina; Taudien, Sarah; Lollies, Anna; Ronge, Viola; Drees, Britta; Lindemann, Monika; Hillen, Uwe; Engler, Harald; Singer, Bernhard B.; Küppers, Ralf

doi:10.1073/pnas.1416276112

Cited by 185 publications

(228 citation statements)

References 74 publications

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“…We have previously shown that, in contrast to vaccination with PCV13, which resulted in an increase of levels of antigen-specific memory B cells (MBCs), in splenectomized subjects with ␤-thalassemia, a history of previous vaccinations with PPV23 had an attenuating effect on antigen-specific MBC pool levels (60). Our findings are in accordance with recent data from studies in murine models as well as in human lymphocytes which have shown that, upon secondary challenge with a T-independent antigen, such as the anti- (71)(72)(73). The proposed mechanisms for the effect of PPV23 on the antigen-specific memory B-cell pool and in relation to previous or subsequent vaccination with a pneumococcal conjugate vaccine are illustrated in Fig.…”

Section: Immunological Hyporesponsivenesssupporting

confidence: 92%

Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

Papadatou

Spoulou

2016

Clin Vaccine Immunol

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Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals. Streptococcus pneumoniae (the pneumococcus) is a major cause of life-threatening invasive infections accounting for considerable morbidity and mortality worldwide (1). Children and adults with certain medical conditions as well as the elderly are at increased risk for invasive pneumococcal disease (IPD) and pneumonia, with disease rates up to 20 times higher than those in the general population (2). High-risk groups consist of children and adults with chronic diseases and with primary and secondary immune deficiencies and of persons with functional or anatomical asplenia. Persons older than 65 years of age are also at increased risk for pneumococcal infection, due to attenuation of their immune response caused by advancing age, a phenomenon called immunosenescence (3). The number of patients in need for protection against IPD is continually increasing due to rising numbers of people with chronic disease or HIV infection and an aging population in many high-income countries.Pneumococcal disease is usually more severe in such high-risk individuals than in immunocompetent subjects (4-6). While antibiotic resistance represents an additional hurdle for the successful treatment of pneumococcal infections (7, 8), optimal protection of such "high-risk" groups against S. pneumoniae infection through vaccination continues to be an important priority.For more than 2 decades, a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been recommended for the protection of immunocompromised individuals and the elderly against invasive pneumococcal disease (IPD) and pneumonia (9).The licensure of the pneumococcal polysaccharide vaccine (PPV) was based on trials of a 6-valent ...

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Section: Immunological Hyporesponsivenesssupporting

confidence: 92%

Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

Papadatou

Spoulou

2016

Clin Vaccine Immunol

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“…Our data is in line with previous reports showing deficiency in CD27+IgD+ cells in SLE [18,19], though in contrast to earlier study [18], we did not see any association of B-cell NSM percentage with disease activity status. The subset of NSM B-cells has been implicated in immune responses against T-cell independent antigens, however recent studies confirmed their role as a long-lasting memory to T-cell dependent antigens involved in reconstitution of switched memory pool upon antigen restimulation [10]. Changes in NSM fraction were accompanied by increased percentage of immature/ /early-transitional B-cells and activated SM cells, both [8,16,23].…”

Section: Discussionmentioning

confidence: 97%

“…But autoreactive B-cells are only a tiny fraction of all memory cells, so why the whole compartment is changed? Some hints came from recent study, showing that various neutrophil-derived proinflammatory mediators facilitate differentiation of IgD+ CD27+ memory B-cells and IgG class switch [10]. Neutrophils participate in the pathogenesis of LN, and both neutrophil derived cytokines (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…IgM+) memory cells (NSM; CD27+IgD+) [8]. During secondary antigen exposure SM B-cells proliferate rapidly and differentiate into antibody secreting cells, while NSM cells are able to reinitiate GC reaction and replenish SM fraction [9,10]. Because B-cell response to nuclear auto-antigens requires T-cell help, formation of pathogenic autoantibodies in SLE (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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Introduction. Renal involvement in systemic lupus erythematosus (SLE) is associated with production of antibodies to double stranded DNA, deposition of immune complexes and organ damage. These processes have been linked with abnormalities in B-and T-cell memory compartments. The aim of the study was to analyze subsets of peripheral memory B-cells and T-cells in lupus nephritis (LN) patients. Material and methods. We used multicolor flow cytometry to analyze major memory subsets of peripheral blood B-cells (defined by CD27, IgD and CD21) and T-cells (CD45RA, CD45RO, CCR7) in 32 patients with active or inactive LN, and 23 control subjects. Results. Lupus nephritis patients were characterized by increased percentage of immature/early-transitional B-cells (CD27-IgD+CD21-), higher frequency of activated switched memory (SM, CD27+IgD-CD21-) and exhausted memory B-cells (CD27-IgD-), and decrease in non-switched memory (NSM, CD27+IgD+) B-cells. CD21 low subsets (immature and activated B-cells) were particularly expanded in patients with active disease. In both groups of LN patients we observed decline in the absolute count of NSM B-cells. It was paralleled by lymphopenia in naïve CD4+ T-cell compartment and increase in the frequency of effector memory T-cells, and these changes were more pronounced in active LN. Conclusions. B-cell memory compartment in LN is deficient in NSM cells and during active disease it is further skewed towards SM and exhausted memory phenotypes, most likely as a cause of chronic antigenic stimulation. Parallel changes in T-helper cell subsets suggest a similar mechanism of SLE-related lymphopenia for both B-cell and T-cell compartment.

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“…Indeed, murine and also human IgM memory B cells preferentially reenter GC reactions (37,42), although also IgG memory B cells have this capacity (43). Some clones are characterized by many individual mutations per clone member (Fig.…”

Section: Cd27mentioning

confidence: 98%

Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers

Budeus

Reynoso²,

Przekopowitz³

et al. 2015

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

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Our knowledge about the clonal composition and intraclonal diversity of the human memory B-cell compartment and the relationship between memory B-cell subsets is still limited, although these are central issues for our understanding of adaptive immunity. We performed a deep sequencing analysis of rearranged immunoglobulin (Ig) heavy chain genes from biological replicates, covering more than 100,000 memory B lymphocytes from two healthy adults. We reveal a highly similar B-cell receptor repertoire among the four main human IgM + and IgG + memory B-cell subsets. Strikingly, in both donors, 45% of sequences could be assigned to expanded clones, demonstrating that the human memory B-cell compartment is characterized by many, often very large, B-cell clones. Twenty percent of the clones consisted of class switched and IgM

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Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions

Cited by 185 publications

References 74 publications

Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

Changes of memory B- and T-cell subsets in lupus nephritis patients

Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers

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