Requirement for BAFF and APRIL during B cell development in GALT

J Immunol. 2010 May 15;184(10):5527-36. doi: 10.4049/jimmunol.1000146. Epub 2010 Apr 16.

Abstract

The effects of B cell-activating factor belonging to the TNF family (BAFF) on B cell maturation and survival in the mouse are relatively well understood. In contrast, little is known about the role of BAFF in B cell development in other mammals, such as rabbits, that use GALT to develop and maintain the B cell compartment. We examined the expression and requirement of BAFF and a proliferation-inducing ligand (APRIL) during peripheral B cell development in young rabbits. By neutralizing BAFF and APRIL in neonates with a soluble decoy receptor, transmembrane activator calcium modulator and cyclophilin ligand interactor-Fc, we found a marked reduction in the number of peripheral B cells, but found no change in the bone marrow (BM) compartment. In the appendix, the size and number of proliferating B cell follicles were greatly reduced, demonstrating that although BAFF/APRIL is dispensable for B cell development in BM, it is required for B cell development in GALT. We found that all rabbit B cells expressed BAFF receptor 3, but did not bind rBAFF, suggesting that the BAFF-binding receptors (BBRs) are bound by endogenous soluble BAFF. Further, we found that B cells themselves express BAFF, suggesting that the soluble BAFF bound to BBRs may be endogenously produced and stimulate B cells in an autocrine fashion. Additionally, we propose that this chronic occupancy of BBRs on B cells may provide a tonic and/or survival signal for the maintenance of peripheral B cells in adults after B lymphopoiesis is arrested in BM.

Publication types

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

MeSH terms

  • Aging / immunology
  • Animals
  • Animals, Newborn
  • B-Cell Activating Factor / biosynthesis
  • B-Cell Activating Factor / metabolism
  • B-Cell Activating Factor / physiology*
  • B-Cell Activation Factor Receptor / biosynthesis
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • CHO Cells
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Proliferation
  • Cricetinae
  • Cricetulus
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Humans
  • Ligands
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Lymphopoiesis / immunology
  • Rabbits
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology*

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Ligands
  • Tumor Necrosis Factor Ligand Superfamily Member 13