Low immunoglobulin M memory B-cell percentage in patients with heterotaxy syndrome correlates with the risk of severe bacterial infection

Chiu, Shuenn–Nan; Shao, Pei-Lan; Wang, Jou‐Kou; Hsu, Hong–Yuan; Lin, Min; Chang, Luan‐Yin; Lu, Chun‐Yi; Lee, Ping–Ing; Huang, Li‐Min; Wu, Mei‐Hwan

doi:10.1038/pr.2015.221

Cited by 12 publications

(8 citation statements)

References 28 publications

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“…Unswitched human MBCs are known to be located in the splenic marginal zone, whereas switched MBCs are found in the perifollicular zone (19, 20); our results predict that a significant measure of their positional specificity is mediated by ligation to VCAM-1 expressed in these zones (4), and by inference also ICAM-1. For the unswitched MBCs, which depend on the spleen for their generation and survival (8, 21, 22), this receptor-ligand pairing may even be of developmental importance. The enhancement of adhesion capacity of both unswitched and switched MBCs over naïve B cells that we demonstrate is likely to reflect the differential importance for the two subsets of staying in one place.…”

Section: Discussionmentioning

confidence: 99%

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

et al. 2019

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Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans.

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Section: Discussionmentioning

confidence: 99%

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

et al. 2019

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“…Another limitation is that we did not look at specific immune cell subsets. A recent study by Chiu et al demonstrated that low number of IgM memory B cells is an independent risk factor for infection in those with isomerism, but we were unable to study this effect as we do not routinely characterise immune cell populations 49 …”

Section: Discussionmentioning

confidence: 94%

“…A recent study by Chiu et al demonstrated that low number of IgM memory B cells is an independent risk factor for infection in those with isomerism, but we were unable to study this effect as we do not routinely characterise immune cell populations. 49 The strengths of our study include the assessment of a large number of patients over a long period of follow-up, as well as a complete description of the types of bacteria and their antibiotic susceptibilities. The inclusions of detailed phenotypic variations in splenic and visceral anatomy are important and also novel.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing bacteraemia in patients with isomerism and CHD: the effects of functional splenic status and antibiotic prophylaxis

2016

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“…Patients with pulmonary atresia and obstructed anomalous pulmonary venous connections are known to be at particularly high risk [24]. The increased risk of bacteremia is likely due to splenic dysfunction and alterations in B-cell populations, further compounded by the presence of invasive monitoring lines and endotracheal tubes [25,26].…”

Section: Discussionmentioning

confidence: 99%

Predictors of Mortality in Patients with Isomerism

Loomba¹,

Frommelt²,

Anderson³

2016

J Pediatr Care

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Low immunoglobulin M memory B-cell percentage in patients with heterotaxy syndrome correlates with the risk of severe bacterial infection

Cited by 12 publications

References 28 publications

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Factors influencing bacteraemia in patients with isomerism and CHD: the effects of functional splenic status and antibiotic prophylaxis

Predictors of Mortality in Patients with Isomerism

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