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Normal B cell homeostasis requires B cell activation factor production by radiation-resistant cells.

Gorelik L, Gilbride K, Dobles M, Kalled SL, Zandman D, Scott ML - J. Exp. Med. (2003)

Bottom Line: On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells.Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis.Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.

View Article: PubMed Central - PubMed

Affiliation: Biogen Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Leonid_Gorelik@biogen.com

ABSTRACT
The cellular source of B cell activation factor (BAFF) required for peripheral B cell survival/maturation is unknown. To determine the nature of BAFF-producing cells we established and analyzed reciprocal bone marrow (BM) chimeras with wild-type (WT) and BAFF-deficient mice. The results revealed that BAFF production by radiation-resistant stromal cells is completely sufficient to provide a necessary signal for B cell survival/maturation, as BAFF-/- BM cells transferred into lethally irradiated WT mice gave rise to normal numbers of follicular (FO) and marginal zone (MZ) B cell subpopulations. On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells. Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis. Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.

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Related in: MedlinePlus

Organization of the splenic B cell follicle in spleen requires BAFF+/+ stroma. Frozen sections of spleens from different chimeras were stained with anti-CD19 (green) and anti-CD4 plus anti-CD8 (red; top), anti-IgM (green), anti-IgD (red), and anti-CD11c plus CD11b (blue; middle), or anti–MOMA-1 (green) and anti-B220 (red). Images of one representative section out of five spleens per group are shown. ×200.
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fig3: Organization of the splenic B cell follicle in spleen requires BAFF+/+ stroma. Frozen sections of spleens from different chimeras were stained with anti-CD19 (green) and anti-CD4 plus anti-CD8 (red; top), anti-IgM (green), anti-IgD (red), and anti-CD11c plus CD11b (blue; middle), or anti–MOMA-1 (green) and anti-B220 (red). Images of one representative section out of five spleens per group are shown. ×200.

Mentions: Immunofluorescent staining of spleen sections from chimeric and BAFF-deficient mice (Fig. 3) supported the data derived by FACS® analysis. BAFF production by stromal cells alone (KO→WT) leads to reconstitution of the white pulp with a normal proportion of B and T cells. In the presence of only the BM cell–derived BAFF (WT→KO), as a consequence of the reduced B cell zone the white pulp area is smaller than normal, and mostly consists of T cells similar to that observed in BAFF-deficient mice. IgD+ B cells are clearly more prevalent in WT→KO chimeras than in BAFF-deficient mice, whereas IgMhigh MZ B cells were just as scant. Interestingly, all mature IgD+ B cells in WT→KO chimeras are aligned along BAFF+/+macrophages and DCs (CD11c+ and CD11b+) that surround the follicle. Staining for MZ B cells using markers for B cells (B220) and metallophilic macrophages (MOMA-1), which delineates the MZ from FO area, confirms the paucity of MZ B cells in WT→KO mice (Fig. 3, bottom).


Normal B cell homeostasis requires B cell activation factor production by radiation-resistant cells.

Gorelik L, Gilbride K, Dobles M, Kalled SL, Zandman D, Scott ML - J. Exp. Med. (2003)

Organization of the splenic B cell follicle in spleen requires BAFF+/+ stroma. Frozen sections of spleens from different chimeras were stained with anti-CD19 (green) and anti-CD4 plus anti-CD8 (red; top), anti-IgM (green), anti-IgD (red), and anti-CD11c plus CD11b (blue; middle), or anti–MOMA-1 (green) and anti-B220 (red). Images of one representative section out of five spleens per group are shown. ×200.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194202&req=5

fig3: Organization of the splenic B cell follicle in spleen requires BAFF+/+ stroma. Frozen sections of spleens from different chimeras were stained with anti-CD19 (green) and anti-CD4 plus anti-CD8 (red; top), anti-IgM (green), anti-IgD (red), and anti-CD11c plus CD11b (blue; middle), or anti–MOMA-1 (green) and anti-B220 (red). Images of one representative section out of five spleens per group are shown. ×200.
Mentions: Immunofluorescent staining of spleen sections from chimeric and BAFF-deficient mice (Fig. 3) supported the data derived by FACS® analysis. BAFF production by stromal cells alone (KO→WT) leads to reconstitution of the white pulp with a normal proportion of B and T cells. In the presence of only the BM cell–derived BAFF (WT→KO), as a consequence of the reduced B cell zone the white pulp area is smaller than normal, and mostly consists of T cells similar to that observed in BAFF-deficient mice. IgD+ B cells are clearly more prevalent in WT→KO chimeras than in BAFF-deficient mice, whereas IgMhigh MZ B cells were just as scant. Interestingly, all mature IgD+ B cells in WT→KO chimeras are aligned along BAFF+/+macrophages and DCs (CD11c+ and CD11b+) that surround the follicle. Staining for MZ B cells using markers for B cells (B220) and metallophilic macrophages (MOMA-1), which delineates the MZ from FO area, confirms the paucity of MZ B cells in WT→KO mice (Fig. 3, bottom).

Bottom Line: On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells.Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis.Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.

View Article: PubMed Central - PubMed

Affiliation: Biogen Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Leonid_Gorelik@biogen.com

ABSTRACT
The cellular source of B cell activation factor (BAFF) required for peripheral B cell survival/maturation is unknown. To determine the nature of BAFF-producing cells we established and analyzed reciprocal bone marrow (BM) chimeras with wild-type (WT) and BAFF-deficient mice. The results revealed that BAFF production by radiation-resistant stromal cells is completely sufficient to provide a necessary signal for B cell survival/maturation, as BAFF-/- BM cells transferred into lethally irradiated WT mice gave rise to normal numbers of follicular (FO) and marginal zone (MZ) B cell subpopulations. On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells. Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis. Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.

Show MeSH
Related in: MedlinePlus