CD4+ T cells promote antibody production but not sustained affinity maturation during Borrelia burgdorferi infection

Infect Immun. 2015 Jan;83(1):48-56. doi: 10.1128/IAI.02471-14. Epub 2014 Oct 13.


CD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response to Borrelia burgdorferi appears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality of B. burgdorferi infection-induced CD4 T(FH) cells. We report that CD4 T cells were effectively primed and T(FH) cells induced after B. burgdorferi infection. These CD4 T cells contributed to the control of B. burgdorferi burden and supported the induction of B. burgdorferi-specific IgG responses. However, while affinity maturation of antibodies against a prototypic T-dependent B. burgdorferi protein, Arthritis-related protein (Arp), were initiated, these increases were reversed later, coinciding with the previously observed involution of germinal centers. The cessation of affinity maturation was not due to the appearance of inhibitory or exhausted CD4 T cells or a strong induction of regulatory T cells. In vitro T-B cocultures demonstrated that T cells isolated from B. burgdorferi-infected but not B. burgdorferi-immunized mice supported the rapid differentiation of B cells into antibody-secreting plasma cells rather than continued proliferation, mirroring the induction of rapid short-lived instead of long-lived T-dependent antibody responses in vivo. The data further suggest that B. burgdorferi infection drives the humoral response away from protective, high-affinity, and long-lived antibody responses and toward the rapid induction of strongly induced, short-lived antibodies of limited efficacy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood*
  • Antibody Affinity
  • Antibody Formation
  • B-Lymphocytes / immunology
  • Borrelia burgdorferi / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Disease Models, Animal
  • Female
  • Immunoglobulin M / blood
  • Lyme Disease / immunology*
  • Male
  • Mice, Inbred BALB C


  • Antibodies, Bacterial
  • Immunoglobulin M