B cells regulate antibody responses through the medullary remodeling of inflamed lymph nodes

Int Immunol. 2012 Jan;24(1):17-27. doi: 10.1093/intimm/dxr089. Epub 2011 Dec 20.

Abstract

Lymph node (LN) structure is remodeled during immune responses, a process which is considered to play an important role in the regulation of immune function. To date, little attention has been paid to the remodeling of the medullary region, despite its proposed role as a niche for antibody-producing plasma cells. Here, we show that B cells mediate medullary remodeling of antigen-draining LNs during inflammation. This process occurs with kinetics similar to changes in plasma cell number and is accompanied by stromal renetworking which manifests as the segregation of B cells and plasma cells. Medullary remodeling depends on signaling via the lymphotoxin-β receptor and the presence of B cells but occurs independently of T-dependent humoral responses or other immune cell subsets including T cells, monocytes and neutrophils. Moreover, reconstitution of non-cognate polyclonal B cells in B cell-deficient mice restores not only the medullary remodeling but also the antibody response by separately transferred cognate B cells, suggesting that non-cognate B cells contribute to antibody responses through medullary remodeling. We propose that non-cognate B cells mediate the expansion of the plasma cell niche in LN through medullary remodeling, thereby regulating the size of the LN plasma cell pool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibody Formation / immunology*
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / transplantation
  • Female
  • Gene Expression
  • Immunization / methods
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphotoxin beta Receptor / genetics
  • Lymphotoxin beta Receptor / immunology*
  • Lymphotoxin beta Receptor / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Confocal
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism

Substances

  • B-Cell Activating Factor
  • Lymphotoxin beta Receptor
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13