Spontaneous follicular exclusion of SHP1-deficient B cells is conditional on the presence of competitor wild-type B cells

J Exp Med. 1998 Mar 16;187(6):929-37. doi: 10.1084/jem.187.6.929.

Abstract

Engagement of antigen receptors on mature B lymphocytes is known to block cell entry into lymphoid follicles and promote accumulation in T cell zones, yet the molecular basis for this change in cell distribution is not understood. Previous studies have shown that follicular exclusion requires a threshold level of antigen receptor engagement combined with occupancy of follicles by B cells without equivalent receptor engagement. The possibility has been raised that follicular composition affects B cell positioning by altering the amount of available antigen and the degree of receptor occupancy. Here we show that follicular composition affects migration of mature B cells under conditions that are independent of antigen receptor occupancy. B cells deficient in the negative regulatory protein tyrosine phosphatase, SHP1, which have elevated intracellular signaling by the B cell receptor, are shown to accumulate in the T zone in the absence of their specific antigen. Follicular exclusion of SHP1-deficient B cells was found to be conditional on the presence of excess B cells that lack elevated intracellular signaling, and was not due to a failure of SHP-1-deficient cells to mature and express the follicle-homing chemokine receptor Burkitt's lymphoma receptor 1. These findings strongly suggest that signals that are negatively regulated by SHP1 promote B cell localization in T cell zones by reducing competitiveness for follicular entry, and provide further evidence that follicular composition influences the positioning of antigen-engaged B cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • Antigens, Differentiation, B-Lymphocyte / physiology
  • B-Lymphocytes / physiology*
  • Cell Adhesion Molecules*
  • GTP-Binding Proteins / analysis
  • Intracellular Signaling Peptides and Proteins
  • Lectins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / deficiency
  • Protein Tyrosine Phosphatases / physiology*
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine / analysis
  • Sialic Acid Binding Ig-like Lectin 2

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CXCR5 protein, mouse
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Intracellular Signaling Peptides and Proteins
  • Lectins
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Sialic Acid Binding Ig-like Lectin 2
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • GTP-Binding Proteins