CD72, a coreceptor with both positive and negative effects on B lymphocyte development and function

Hsin-Jung Joyce Wu, Subbarao Bondada

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Introduction: B lymphocytes remain in a resting state until activated by antigenic stimuli through interaction with the B cell receptor (BCR). Coreceptors on B cells can modulate the thresholds for signaling through the BCR for growth and differentiation. CD72 is a B cell coreceptor that has been shown to interact with CD100, a semaphorin, and to enhance BCR signaling. Discussion: CD72 ligation induces a variety of early signaling events such as activation of the Src kinases Blk and Lyn and the non-src kinase Btk leading to activation of the mitogen-activated protein (MAP) kinases, events usually associated with positive signaling. CD72 signals can enable Btk-deficient B cells to overcome their unresponsiveness to BCR signaling. On the other hand, BCR-mediated signals are enhanced in CD72-deficient cells but are reduced in CD100 null cells. The dual effects of CD72 on B cells can be explained by its association with positive and negative signaling molecules. Thus, CD72 interacts with SHP-1, an SH2-domain containing protein tyrosine phosphatase, a negative regulator of signaling, and Grb2, an adaptor protein associated with the Ras/MAPK pathway. Ligation of CD72 also triggered its association with CD19, a positive modulator of B cell receptor signaling. We propose a dual signaling hypothesis to explain the growth and differentiation promoting properties of CD72. Deficiency in either CD72 or CD100 leads to autoimmunity in mouse models. CD72 expression and polymorphisms exhibit some association with autoimmune diseases such as lupus, Sjogren's syndrome, and type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalJournal of Clinical Immunology
Volume29
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

B-Lymphocytes
Ligation
SH2 Domain-Containing Protein Tyrosine Phosphatases
Null Lymphocytes
src-Family Kinases
Sjogren's Syndrome
Growth
Mitogen-Activated Protein Kinases
Autoimmunity
Type 1 Diabetes Mellitus
Autoimmune Diseases
Phosphotransferases

Keywords

  • Antibody response
  • Apoptosis
  • Autoimmunity
  • B cell
  • B cell receptor
  • CD100
  • CD72
  • Differentiation
  • ITIM motifs
  • Proliferation
  • Protein tyrosine kinase
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

CD72, a coreceptor with both positive and negative effects on B lymphocyte development and function. / Wu, Hsin-Jung Joyce; Bondada, Subbarao.

In: Journal of Clinical Immunology, Vol. 29, No. 1, 01.2009, p. 12-21.

Research output: Contribution to journalArticle

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