Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa

Front Immunol. 2018 Sep 7;9:1976. doi: 10.3389/fimmu.2018.01976. eCollection 2018.

Abstract

The efficacy of the adaptive humoral immune response likely requires diverse, yet focused regional B cell antibody production throughout the body. Here we address, in the first study of its kind, the B cell repertoire in the bronchial mucosa, an important barrier to antigens inhaled from the atmosphere. To accomplish this, we have applied high-throughput Adaptive Immune Receptor Repertoire Sequencing (AIRR-Seq) to 10 bronchial biopsies from altogether four different sites in the right lungs from an asthmatic patient and a healthy subject. While the majority of identified B cell clones were restricted to a single site, many were disseminated in multiple sites. Members of a clone were shared more between adjacent biopsies than between distal biopsies, suggesting local mucosal migration and/or a homing mechanism for B cells through the blood or lymph. A smaller fraction of clones spanned the bronchial mucosa and peripheral blood, suggesting ongoing trafficking between these compartments. The bronchial mucosal B cell repertoire in the asthmatic patient was geographically more variable but less diverse compared to that of the healthy subject, suggesting an ongoing, antigen-driven humoral immune response in atopic asthma. Whether this is a feature of atopy or disease status remains to be clarified in future studies. We observed a subset of highly mutated and antigen-selected IgD-only cells in the bronchial mucosa. These cells were found in relative high abundance in the asthmatic individual but also, albeit at lower abundance, in the healthy subject. This novel finding merits further exploration using a larger cohort of subjects.

Keywords: B-cell antibody repertoire; asthma; bronchial mucosa; cell trafficking; clonal dissemination; next generation sequencing; somatic hypermutation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Movement
  • Clonal Evolution / immunology*
  • Clonal Selection, Antigen-Mediated* / genetics
  • Clonal Selection, Antigen-Mediated* / immunology
  • Humans
  • Immunoglobulin Isotypes / genetics
  • Immunoglobulin Isotypes / immunology
  • Lymphocyte Count
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Somatic Hypermutation, Immunoglobulin

Substances

  • Immunoglobulin Isotypes