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 language | English (US) |
|---|---|
| Pages (from-to) | 12-21 |
| Number of pages | 10 |
| Journal | Journal of Clinical Immunology |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - CD72, a coreceptor with both positive and negative effects on B lymphocyte development and function
AU - Wu, Hsin-Jung Joyce
AU - Bondada, Subbarao
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Antibody response
KW - Apoptosis
KW - Autoimmunity
KW - B cell
KW - B cell receptor
KW - CD100
KW - CD72
KW - Differentiation
KW - ITIM motifs
KW - Proliferation
KW - Protein tyrosine kinase
KW - Protein tyrosine phosphatase
UR - http://www.scopus.com/inward/record.url?scp=59449090709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59449090709&partnerID=8YFLogxK
U2 - 10.1007/s10875-008-9264-6
DO - 10.1007/s10875-008-9264-6
M3 - Article
C2 - 19067131
AN - SCOPUS:59449090709
VL - 29
SP - 12
EP - 21
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
SN - 0271-9142
IS - 1
ER -