Lymphoadenopathy During Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation

PLoS Pathog. 2011 May;7(5):e1002066. doi: 10.1371/journal.ppat.1002066. Epub 2011 May 26.

Abstract

Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy. The ensuing lymph node response is characterized by strong, rapid extrafollicular B cell proliferation and differentiation to plasma cells, as assessed by immunohistochemistry, flow cytometry and ELISPOT analysis, while germinal center reactions were not consistently observed. The extrafollicular nature of this B cell response and its strongly IgM-skewed isotype profile bear the hallmarks of a T-independent response. The induced B cell response does appear, however, to be largely antigen-specific. Use of a cocktail of recombinant, in vivo-expressed B. burgdorferi-antigens revealed the robust induction of borrelia-specific antibody-secreting cells by ELISPOT. Furthermore, nearly a quarter of hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens. Finally, neither the quality nor the magnitude of the B cell responses was altered in mice lacking the Toll-like receptor adaptor molecule MyD88. Together, these findings suggest a novel evasion strategy for B. burgdorferi: subversion of the quality of a strongly induced, potentially protective borrelia-specific antibody response via B. burdorferi's accumulation in lymph nodes.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Bacterial / metabolism
  • Antigens, Bacterial / metabolism
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / microbiology*
  • B-Lymphocytes / pathology*
  • Borrelia burgdorferi / isolation & purification
  • Borrelia burgdorferi / physiology*
  • Cell Proliferation*
  • Disease Models, Animal
  • Female
  • Lyme Disease / complications*
  • Lyme Disease / metabolism
  • Lyme Disease / pathology
  • Lymph Nodes / metabolism
  • Lymph Nodes / microbiology
  • Lymph Nodes / pathology
  • Lymphatic Diseases / metabolism
  • Lymphatic Diseases / microbiology*
  • Lymphatic Diseases / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Myeloid Differentiation Factor 88 / metabolism
  • Spirochaetales / immunology
  • Spirochaetales / physiology*
  • Ticks / microbiology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Myeloid Differentiation Factor 88