Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone children

Basha, Saleem; Pichichero, Michael E.

doi:10.1111/cei.12660

Cited by 17 publications

(17 citation statements)

References 33 publications

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“…19 We found similar proportions of CD19 + B cells in the lymphocyte population in both groups of children but significantly lower percentages of memory CD19 + CD27 + B cells in sOP children. The frequencies of DT, TT or PT-specific memory B cells in sOP children were significantly lower compared to NOP children.…”

Section: Adaptive Immune Cell Responsessupporting

confidence: 50%

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Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

Pichichero

2016

Pediatric Infectious Disease Journal

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This review summarizes a prospective, longitudinal 10-year study in Rochester NY with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently-defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often RSV infection led to AOM in sOP than non-otitis prone (NOP) children that correlated with diminished total RSV-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following NP colonization and AOM than NOP children and they had defects in antigen presenting cells.

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Section: Adaptive Immune Cell Responsessupporting

confidence: 50%

“…This is in agreement with earlier reports that antigen-specific memory B cells persist years after vaccination and correlate with humoral immunity. 19 …”

Section: Adaptive Immune Cell Responsesmentioning

confidence: 99%

Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

Pichichero

2016

Pediatric Infectious Disease Journal

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“…As shown in Fig. 3b , the percentage of CD27 + CD19 + CD4 − memory B cells [ 16 – 18 ] in acute schistosomiasis patients was significantly higher than in HCs ( t (20) = 2.250, P = 0.036). In contrast, the percentage of CD27 − CD19 + CD4 − naïve B cells [ 19 ] in patients was lower than in the HCs (Fig.…”

Section: Resultsmentioning

confidence: 90%

T follicular helper cells in patients with acute schistosomiasis

et al. 2016

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BackgroundThe role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. In a previous study, a higher frequency of circulating PD-1+CXCR5+CD4+ Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. However, the function of Tfh cells in patients with acute schistosomiasis remains elusive; this was investigated in the present study.MethodsThe frequency of circulating Tfh cells and the expression of inducible T cell co-stimulator (ICOS), programmed cell death 1 (PD-1) and B cell subsets were analyzed in 12 patients with acute schistosomiasis and 10 HCs by flow cytometry. The expression of Bcl6, c-Maf and IL-21 mRNA were detected by quantitative real-time reverse transcriptase PCR (qRT-PCR). The concentration of serum IL-21 and IgG specific to Schistosoma japonicum antigen were then determined by enzyme linked immunosorbent assay (ELISA). Correlations between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum were analyzed by Spearman’s rank correlation.ResultsThe frequency of PD-1+CXCR5+CD4+ Tfh and memory B cells was increased in acute schistosomiasis patients relative to HCs. Moreover, the levels of IL-21 in serum and the expression of IL-21 mRNA were higher in acute schistosomiasis patients. However, there was no significant correlation between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum antigen in patients with acute schistosomiasis.ConclusionsPD-1+CXCR5+CD4+ Tfh cells in peripheral blood are involved in the immune response of patients with acute schistosomiasis. Understanding the immunological mechanism is helpful for the development of vaccination strategies to control schistosomiasis.

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“…Given the roles of Tfh cells in providing help to B cells, we next characterized the frequencies of different subsets of B cells by flow cytometry analysis. As shown in Fig 3 , the percentages of CD27 + CD19 + CD3 - CD4 - memory B cells [ 23 – 25 ], CD86 + CD19 + CD3 - CD4 - activated B cells [ 26 – 28 ], and CD38 ++ CD19 + CD3 - CD4 - plasma cells [ 29 – 31 ] in schistosomiasis patients were significantly greater than those in the HCs, although the percentage of total B cells was slightly decreased in patients with schistosomiasis. In contrast, the percentage of CD27 - CD19 + CD3 - CD4 - naïve B cells [ 32 ] in patients was less than that in the HCs ( Fig 3C ).…”

Section: Resultsmentioning

confidence: 99%

Distribution of Peripheral Memory T Follicular Helper Cells in Patients with Schistosomiasis Japonica

Chen

Zhang

et al. 2015

PLoS Negl Trop Dis

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BackgroundSchistosomiasis is a helminthic disease that affects more than 200 million people. An effective vaccine would be a major step towards eliminating the disease. Studies suggest that T follicular helper (Tfh) cells provide help to B cells to generate the long-term humoral immunity, which would be a crucial component of successful vaccines. Thus, understanding the biological characteristics of Tfh cells in patients with schistosomiasis, which has never been explored, is essential for vaccine design.Methodology/Principal FindingsIn this study, we investigated the biological characteristics of peripheral memory Tfh cells in schistosomiasis patients by flow cytometry. Our data showed that the frequencies of total and activated peripheral memory Tfh cells in patients were significantly increased during Schistosoma japonicum infection. Moreover, Tfh2 cells, which were reported to be a specific subpopulation to facilitate the generation of protective antibodies, were increased more greatly than other subpopulations of total peripheral memory Tfh cells in patients with schistosomiasis japonica. More importantly, our result showed significant correlations of the percentage of Tfh2 cells with both the frequency of plasma cells and the level of IgG antibody. In addition, our results showed that the percentage of T follicular regulatory (Tfr) cells was also increased in patients with schistosomiasis.Conclusions/SignificanceOur report is the first characterization of peripheral memory Tfh cells in schistosomasis patients, which not only provides potential targets to improve immune response to vaccination, but also is important for the development of vaccination strategies to control schistosomiasis.

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Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone children

Cited by 17 publications

References 33 publications

Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

T follicular helper cells in patients with acute schistosomiasis

Distribution of Peripheral Memory T Follicular Helper Cells in Patients with Schistosomiasis Japonica

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