Regulation of Aged Humoral Immune Defense against Pneumococcal Bacteria by IgM Memory B Cell

Shi, Yan; Yamazaki, Takashi; Okubo, Yoshio; Uehara, Yoshio; Sugane, Kazuo; Agematsu, Kazunaga

doi:10.4049/jimmunol.175.5.3262

Cited by 211 publications

(195 citation statements)

References 34 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…memory B cells in old subjects (Table 2). This is in agreement with previous data that have demonstrated a reduction of IgM ''only'' memory B cells in the elderly (Shi et al 2005). We show a slight increase in the expression of IgG and IgA on switched memory B cells but this did not reach significance, although the relative proportions of the different isotypes of memory cells mirrors the relative proportion of serum immunoglobulin of the different isotypes (Paganelli et al 1992;Listì et al 2006).…”

Section: Surface Immunoglobulin Of Dn Cellssupporting

confidence: 94%

See 1 more Smart Citation

B cell immunosenescence: different features of naive and memory B cells in elderly

et al. 2011

View full text Add to dashboard Cite

Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/naïve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro-and anti-inflammatory cytokines, tumor necrosis factor (TNF)-a and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG ? IgD -CD27 -double negative (DN) B cells that are expanded in the elderly. Our results show that naïve B cells from young donors need a sufficiently strong stimulus to be activated ''in vitro'', while naïve B cells from old subjects are able to produce IL-10 and TNF-a when stimulated ''physiologically'' (a-CD40/IL-4), suggesting that these cells might play a role in the control of the immuno-inflammatory environment in the elderly. In addition, in the elderly there is an accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN B lymphocytes may be exhausted cells that are expanded and accumulate as a by-product of persistent stimulation or impaired germinal center formation.

show abstract

Section: Surface Immunoglobulin Of Dn Cellssupporting

confidence: 94%

“…IgD -CD27 ? ) memory B cells in old subjects (Shi et al 2005), although the compensatory increase in the expression of IgG and IgA on switched memory CD27 ? B cells did not reach significance.…”

Section: Discussionmentioning

confidence: 94%

B cell immunosenescence: different features of naive and memory B cells in elderly

et al. 2011

View full text Add to dashboard Cite

show abstract

“…2D). The highly mutated IgD sequences may stem either from atypical IgD + IgM + memory cells expressing both IgM and IgD via alternative splicing (26)(27)(28)(29) or from rare IgM − IgD + B cells having entirely class-switched to IgD via genetic recombination (26,30). We noted that an appreciable percentage of VDJ sequences with the IgD isotype was absent from the IgM isotype in oligoclonal participants' superlineages ( Fig.…”

Section: Resultsmentioning

confidence: 84%

Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging

Bourcy

Angel

Vollmers

et al. 2017

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

118

123

View full text Add to dashboard Cite

The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic. In 50% of the elderly individuals, a large space in the repertoire was occupied by a small number of recall lineages that did not decline during vaccine response and contained hypermutated IgD + B cells. Relative to their younger counterparts, older subjects demonstrated a contracted naive repertoire and diminished intralineage diversification, signifying a reduced substrate for mounting novel responses and decreased fine-tuning of BCR specificities by somatic hypermutation. Furthermore, a larger proportion of the repertoire exhibited premature stop codons in some elderly subjects, indicating that aging may negatively affect the ability of B cells to discriminate between functional and nonfunctional receptors. Finally, we observed a decreased incidence of radical mutations compared with conservative mutations in elderly subjects' vaccine responses, which suggests that accumulating original antigenic sin may be limiting the accessible space for paratope evolution. Our findings shed light on the complex interplay of environmental and gerontological factors affecting immune senescence, and provide direct molecular characterization of the effects of senescence on the immune repertoire.aging | antibody repertoire | influenza vaccine | CMV | UniFrac T he deterioration of immune function with age, a process referred to as immunosenescence, is well recognized. Notable changes contributing to immunosenescence include, among others, decreased proliferation of lymphocytes, reduced T-cell receptor repertoire, and defects in antibody production (1, 2). This phenomenon contributes to an age-related increase in susceptibility to viral and bacterial infections and decreased response to vaccination (3-5). Indeed, individuals over the age of 65 y are less than half as protected by standard influenza vaccines as younger individuals (6), and pneumonia and influenza represent the fourth most common cause of death among aging individuals (4).Antibody-mediated immunity is the result of an evolutionary arms race between the pathogens to which an individual is exposed and antibody-producing B cells. A tremendous diversity of potential antibody affinities is generated by the mechanisms of V(D)J recombination, random junctional insertions/deletions, and somatic hypermutation (7). Preferential proliferation of activated B cells upon encounter with a cognate antigen then exerts a selective pressure for B-cell receptors (BCRs) with a high binding affinity to the antigen (7). The clonal history of B cells circulating in the blood c...

show abstract

“…In 70% of all HIV patients studied, the percentage of IgM B cells was the same as that seen in individuals who had a history of splenectomy. A significant reduction or absence of IgM memory B cells is also found in other patient groups (the elderly, children under 2 years of age, or patients with congenital asplenia) who have an increased risk of invasive pneumococcal infection (33,34). Further support for the importance of IgM memory B cells in host protection against pneumococcal infection comes from studies of CVID patients which show an association between recurrent chest infections and reduced concentration of pneumococcal IgM Abs and lower IgM memory B cell counts (33,35).…”

Section: Discussionmentioning

confidence: 90%

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

Hart

Steel

Clark

et al. 2007

The Journal of Immunology

153

154

View full text Add to dashboard Cite

Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.

show abstract

Regulation of Aged Humoral Immune Defense against Pneumococcal Bacteria by IgM Memory B Cell

Cited by 211 publications

References 34 publications

B cell immunosenescence: different features of naive and memory B cells in elderly

B cell immunosenescence: different features of naive and memory B cells in elderly

Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

Contact Info

Product

Resources

About