Abstract
The TNF family cytokine B cell-activating factor belonging to the TNF family (BAFF) (BLyS) plays a fundamental role in regulating peripheral B cell survival and homeostasis. A BAFF-specific receptor (BAFF-R; BR3) appears to mediate these functions via activation of the NF-κB2 pathway. Signaling by the BAFF-R is also required to sustain the germinal center (GC) reaction. Engagement of this receptor results in the induction of Bcl-2, suggesting that this antiapoptotic factor acts downstream of the BAFF-R and NF-κB2 pathway to promote peripheral B cell survival during primary and Ag-driven development. To test this idea, we created lines of mice coexpressing a Bcl-2 transgene and a signaling-deficient form of the BAFF-R derived from the B lymphopenic A/WySnJ strain. Surprisingly, although dramatically elevated numbers of B cells accumulate in the periphery of these mice, these B cells exhibit extremely perturbed primary development, formation of lymphoid microenvironments, and GC and IgG responses. Moreover, mice expressing the bcl-2 transgene alone display a loss of marginal zone B cells, an expansion of follicular B cells that appear immature, and alterations of the GC reaction. These results suggest that the BAFF-R and Bcl-2 regulate key and nonoverlapping aspects of peripheral B cell survival and development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6179-6188 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 10 |
| DOIs | |
| State | Published - Nov 15 2004 |
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All Science Journal Classification (ASJC) codes
- Immunology
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B cells expressing Bcl-2 and a signaling-impaired BAFF-specific receptor fail to mature and are deficient in the formation of lymphoid follicles and germinal centers. / Rahman, Ziaur; Manser, Tim.
In: Journal of Immunology, Vol. 173, No. 10, 15.11.2004, p. 6179-6188.Research output: Contribution to journal › Article
TY - JOUR
T1 - B cells expressing Bcl-2 and a signaling-impaired BAFF-specific receptor fail to mature and are deficient in the formation of lymphoid follicles and germinal centers
AU - Rahman, Ziaur
AU - Manser, Tim
PY - 2004/11/15
Y1 - 2004/11/15
N2 - The TNF family cytokine B cell-activating factor belonging to the TNF family (BAFF) (BLyS) plays a fundamental role in regulating peripheral B cell survival and homeostasis. A BAFF-specific receptor (BAFF-R; BR3) appears to mediate these functions via activation of the NF-κB2 pathway. Signaling by the BAFF-R is also required to sustain the germinal center (GC) reaction. Engagement of this receptor results in the induction of Bcl-2, suggesting that this antiapoptotic factor acts downstream of the BAFF-R and NF-κB2 pathway to promote peripheral B cell survival during primary and Ag-driven development. To test this idea, we created lines of mice coexpressing a Bcl-2 transgene and a signaling-deficient form of the BAFF-R derived from the B lymphopenic A/WySnJ strain. Surprisingly, although dramatically elevated numbers of B cells accumulate in the periphery of these mice, these B cells exhibit extremely perturbed primary development, formation of lymphoid microenvironments, and GC and IgG responses. Moreover, mice expressing the bcl-2 transgene alone display a loss of marginal zone B cells, an expansion of follicular B cells that appear immature, and alterations of the GC reaction. These results suggest that the BAFF-R and Bcl-2 regulate key and nonoverlapping aspects of peripheral B cell survival and development.
AB - The TNF family cytokine B cell-activating factor belonging to the TNF family (BAFF) (BLyS) plays a fundamental role in regulating peripheral B cell survival and homeostasis. A BAFF-specific receptor (BAFF-R; BR3) appears to mediate these functions via activation of the NF-κB2 pathway. Signaling by the BAFF-R is also required to sustain the germinal center (GC) reaction. Engagement of this receptor results in the induction of Bcl-2, suggesting that this antiapoptotic factor acts downstream of the BAFF-R and NF-κB2 pathway to promote peripheral B cell survival during primary and Ag-driven development. To test this idea, we created lines of mice coexpressing a Bcl-2 transgene and a signaling-deficient form of the BAFF-R derived from the B lymphopenic A/WySnJ strain. Surprisingly, although dramatically elevated numbers of B cells accumulate in the periphery of these mice, these B cells exhibit extremely perturbed primary development, formation of lymphoid microenvironments, and GC and IgG responses. Moreover, mice expressing the bcl-2 transgene alone display a loss of marginal zone B cells, an expansion of follicular B cells that appear immature, and alterations of the GC reaction. These results suggest that the BAFF-R and Bcl-2 regulate key and nonoverlapping aspects of peripheral B cell survival and development.
UR - http://www.scopus.com/inward/record.url?scp=8444222647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8444222647&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.173.10.6179
DO - 10.4049/jimmunol.173.10.6179
M3 - Article
C2 - 15528355
AN - SCOPUS:8444222647
VL - 173
SP - 6179
EP - 6188
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -