The V gene repertoires of classical and atypical memory B cells in malaria-susceptible West African children

J Immunol. 2015 Feb 1;194(3):929-39. doi: 10.4049/jimmunol.1402168. Epub 2015 Jan 2.

Abstract

Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19(+)/CD20(+)/CD21(+)/CD27(+)/CD10(-)) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19(+)/CD20(+)/CD21(-)/CD27(-)/CD10(-)). At present, the function of atypical MBCs in malaria is not known, nor are the factors that drive their differentiation. To gain insight into the relationship between classical and atypical IgG(+) MBCs, we compared the Ab H and L chain V gene repertoires of children living in a malaria-endemic region in Mali. We found that these repertoires were remarkably similar by a variety of criteria, including V gene usage, rate of somatic hypermutation, and CDR-H3 length and composition. The similarity in these repertoires suggests that classical MBCs and atypical MBCs differentiate in response to similar Ag-dependent selective pressures in malaria-exposed children and that atypical MBCs do not express a unique V gene repertoire.

Publication types

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

MeSH terms

  • Africa, Western
  • Amino Acid Sequence
  • Antigens, Protozoan / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Complementarity Determining Regions / genetics
  • Disease Susceptibility*
  • Female
  • Gene Rearrangement, B-Lymphocyte
  • Genetic Variation
  • Humans
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / chemistry
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics*
  • Immunologic Memory / genetics*
  • Immunophenotyping
  • Malaria / genetics*
  • Malaria / immunology*
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / immunology
  • Male
  • Plasmodium falciparum / immunology
  • Somatic Hypermutation, Immunoglobulin

Substances

  • Antigens, Protozoan
  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region