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Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice.

Rahman ZS, Rao SP, Kalled SL, Manser T - J. Exp. Med. (2003)

Bottom Line: Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development.A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited.In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, and The Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19017-5541, USA.

ABSTRACT
The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development. A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited. A BAFF receptor expressed by B cells (BAFF-R/BR3) is defective in A/WySnJ mice which exhibit a phenotype similar to BAFF-deficient (BAFF-/-) animals. Here, we show that although GC responses can be efficiently induced in both A/WySnJ and BAFF-/- mice, these responses are not sustained. In BAFF-/- mice, this response is rapidly attenuated and accompanied by perturbed follicular dendritic cell development and immune complex trapping. In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response. These data demonstrate a multifaceted role for the BAFF pathway in regulating GC progression.

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(A) In situ BrdU incorporation assay in A/J and A/WySnJ GCs. One of two parallel sections obtained from SRBC-immunized mice was stained (top panel, for day 9 and 14) with anti-IgD (blue) and PNA (red), and the other section (bottom panel, for day 9 and day 14) was stained with anti-BrdU (red). Data are representative of three mice at each time point. (B) PI cell cycle analysis on GC B cells (B220+GL7+IgD−) obtained by FACS® on day 8 post-SRBC immunization. The horizontal bar and number in each panel represent GC B cells that are in S/G2-M phases. These data were obtained from the pooled spleen cells of three A/J and five A/WySnJ mice. Original magnification of images was 25×.
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fig6: (A) In situ BrdU incorporation assay in A/J and A/WySnJ GCs. One of two parallel sections obtained from SRBC-immunized mice was stained (top panel, for day 9 and 14) with anti-IgD (blue) and PNA (red), and the other section (bottom panel, for day 9 and day 14) was stained with anti-BrdU (red). Data are representative of three mice at each time point. (B) PI cell cycle analysis on GC B cells (B220+GL7+IgD−) obtained by FACS® on day 8 post-SRBC immunization. The horizontal bar and number in each panel represent GC B cells that are in S/G2-M phases. These data were obtained from the pooled spleen cells of three A/J and five A/WySnJ mice. Original magnification of images was 25×.

Mentions: GC B cell proliferation in A/WySnJ mice was evaluated using an in situ BrdU incorporation assay. As shown in Fig. 6 A, BrdU-positive cells (reddish-brown, bottom panels, day 9 and 14) reflect proliferating B cells in a PNA+ IgD− GC (red-orange, top panels) revealed in the adjacent section. GC cell BrdU staining frequency and intensity on day 9 were comparable in A/J and A/WySnJ mice. In contrast, very few intensely staining BrdU+ cells were seen in day 14 A/WySnJ GCs.


Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice.

Rahman ZS, Rao SP, Kalled SL, Manser T - J. Exp. Med. (2003)

(A) In situ BrdU incorporation assay in A/J and A/WySnJ GCs. One of two parallel sections obtained from SRBC-immunized mice was stained (top panel, for day 9 and 14) with anti-IgD (blue) and PNA (red), and the other section (bottom panel, for day 9 and day 14) was stained with anti-BrdU (red). Data are representative of three mice at each time point. (B) PI cell cycle analysis on GC B cells (B220+GL7+IgD−) obtained by FACS® on day 8 post-SRBC immunization. The horizontal bar and number in each panel represent GC B cells that are in S/G2-M phases. These data were obtained from the pooled spleen cells of three A/J and five A/WySnJ mice. Original magnification of images was 25×.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194236&req=5

fig6: (A) In situ BrdU incorporation assay in A/J and A/WySnJ GCs. One of two parallel sections obtained from SRBC-immunized mice was stained (top panel, for day 9 and 14) with anti-IgD (blue) and PNA (red), and the other section (bottom panel, for day 9 and day 14) was stained with anti-BrdU (red). Data are representative of three mice at each time point. (B) PI cell cycle analysis on GC B cells (B220+GL7+IgD−) obtained by FACS® on day 8 post-SRBC immunization. The horizontal bar and number in each panel represent GC B cells that are in S/G2-M phases. These data were obtained from the pooled spleen cells of three A/J and five A/WySnJ mice. Original magnification of images was 25×.
Mentions: GC B cell proliferation in A/WySnJ mice was evaluated using an in situ BrdU incorporation assay. As shown in Fig. 6 A, BrdU-positive cells (reddish-brown, bottom panels, day 9 and 14) reflect proliferating B cells in a PNA+ IgD− GC (red-orange, top panels) revealed in the adjacent section. GC cell BrdU staining frequency and intensity on day 9 were comparable in A/J and A/WySnJ mice. In contrast, very few intensely staining BrdU+ cells were seen in day 14 A/WySnJ GCs.

Bottom Line: Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development.A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited.In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, and The Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19017-5541, USA.

ABSTRACT
The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development. A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited. A BAFF receptor expressed by B cells (BAFF-R/BR3) is defective in A/WySnJ mice which exhibit a phenotype similar to BAFF-deficient (BAFF-/-) animals. Here, we show that although GC responses can be efficiently induced in both A/WySnJ and BAFF-/- mice, these responses are not sustained. In BAFF-/- mice, this response is rapidly attenuated and accompanied by perturbed follicular dendritic cell development and immune complex trapping. In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response. These data demonstrate a multifaceted role for the BAFF pathway in regulating GC progression.

Show MeSH
Related in: MedlinePlus