Distinct variations of antibody secreting cells and memory B cells during the course of Kawasaki disease

BMC Immunol. 2019 Jun 3;20(1):16. doi: 10.1186/s12865-019-0299-7.

Abstract

Background: Both antibody secreting cells (ASCs) and memory B cells are essential for the maintenance of humoral immunity. To date, limit studies have focused on the two populations in Kawasaki disease (KD). To address the status of humoral immunity during KD, our current concentration is on the variations of ASCs and memory B cells, as well as their subsets in both acute and remission stages of KD.

Methods: ASCs were defined as the population with high expressions of CD27 and CD38 among CD3-CD20- lymphocytes. Based on the expression of surface marker CD138 and intracellular marker IgG, ASCs were further divided into two subsets. Memory B cells were characterized by the expressions of IgD, CD27 and IgM, upon which memory B cells were further categorized into CD27 + IgD- (switched memory, Sm), CD27-IgD- (Double negative, DN) and CD27 + IgD + IgM+ (marginal zone, MZ) B cells. Collectively, six populations were analyzed using flow cytometry. The blood samples were collected from KD patients in different stages and healthy controls.

Results: In the acute stage, the percentages of ASCs, CD138+ ASCs, and IgG+ ASCs were significantly increased. In contrast, the percentages of memory B cells including Sm and MZ B cells were significantly decreased. Correlation analysis found ASCs positively correlated with the level of serum IgM, whereas MZ B cells not only positively correlated with the level of serum IgG, IgA, and IgM, but also positively correlated with the level of serum complement C3 and C4 and negatively correlated with the value of C-reactive protein (CRP). In the remission stage, the percentages of IgG+ ASCs and MZ B cells were significantly reduced, whereas other subsets presented heterogeneous variations.

Conclusions: Our study provided direct evidence that ASCs contributed to the pathogenesis of KD, and it was the first time to describe the variation of memory B cells in this disease. Among the subsets, only IgG+ ASCs presented a significant increase in the acute stage and decreased after IVIG administration, indicating the involvement of IgG+ ASCs in the inflammation of KD and also suggesting that IVIG played an inhibitory role in the expression of cytoplasmic IgG.

Keywords: Antibody secreting cells; Cytoplasmic IgG; Kawasaki disease; Memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antibody-Producing Cells / immunology*
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Immunity, Humoral
  • Immunologic Memory
  • Infant
  • Male
  • Mucocutaneous Lymph Node Syndrome / immunology*

Substances

  • Antigens, CD