Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: Tailoring better vaccination strategies

Abstract

Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients. Keywords: Asplenia r Memory B cells r Serum anti-PnPS r Splenectomy r Streptococcus pneumoniaeAdditional supporting information may be found in the online version of this article at the publisher's web-site Eur. J. Immunol. 2013Immunol. . 43: 2659Immunol. -2670 Introduction Asplenic patients have an increased susceptibility to bacterial infections that can evolve into severe and often lethal overwhelming postsplenectomy infection (OPSI) [1,2]. Lifetime risk of developing an OPSI is nearly 1-5% and mortality rates range between 40 and 70% [3]. Streptococcus pneumoniae is the most common pathogen causing bacteremia in splenectomized patients, followed by Haemophilus influenzae, Neisseria meningitidis, Escherichia coli, Salmonella, Pseudomonas, and Klebsiella [3,4]. The red pulp of the spleen represents a very important defense from bacteremia. In the red pulp of the spleen, the blood flows slowly in a large net of sinusoids. Macrophages, located among endothelial cells, have the function of removing and destroying particulate antigens, such as bacteria [5][6][7]. In the absence of the spleen, bacteria can therefore accumulate and replicate in the blood causing septic shock.Over the last few years, the role of the spleen in the maintenance of a pool of memory B cells involved in the protection against encapsulated bacteria has been also demonstrated. In particular, we showed that splenectomized patients lack IgM memory B cells [8]. This cell population, also known as marginal zone B cells or effector memory B cells, is produced by a T-independent mechanism [9] and inhabits the marginal zone of the spleen. IgM memory B cells generate the response to pneumococcal polysaccharide (PnP...

B-cell hyperfunction in children with immune thrombocytopenic purpura persists after splenectomy

“…We have shown in previous studies that splenectomy is associated with an extreme reduction of the B-cell memory pool (25,26). In contrast with these observations, in our splenectomized ITP patients, the frequency of memory B cells was in the normal range with a prevalence of switched memory B cells (Figure 4a).…”

“…Splenectomy is performed in ITP patients with the aim of sparing from destruction platelets tagged by autoantibodies. We have shown that the removal of the spleen causes depletion of both IgM and switched memory B cells (Figure 4a, right) (25,26,31). The reduction of IgM memory B cells remains a permanent characteristic of splenectomized individuals, whereas switched memory B cells are slowly regenerated over time (31)(32)(33).…”

“…The response also generates IgG and IgA. Splenectomized individuals have a significant reduction of antipneumococcus IgA and IgG spots (Figure 5c) and also of IgM spots (Figure 5d) (26). In splenectomized ITP patients, IgG and IgA were not reduced and IgM spots were increased as compared with controls and splenectomized adults.…”

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

“…However, various studies have shown that PPS induce efficient activation of IgM + memory B cells (IgM + IgD + CD27 + ) and generation of long-lived plasma cells (CD38 + CD20 low ). This is accompanied by the generation and persistence of IgM and IgG antibodies against PPS [101][102][103][104][105][106][107][108]. IgM + memory B cells circulating in the blood are the peripheral correlates of the marginal zone B cells of the spleen.…”

Practical review of immunizations in adult patients with cancer

“…75 For patients who receive vaccines after splenectomy, the antibody response to the immunizations should be measured to determine the need for booster doses, as studies in children with Hodgkin disease showed poor antibody response to vaccines given after splenectomy. 76 Compared with those of healthy individuals, the immune systems of patients with hyposplenia can mount only a small protective antibody response to polysaccharide antigens, which may result in vaccine failure. Therefore, conjugated vaccines are preferred in these patients.…”