Limits...
Germinal center founder cells display propensity for apoptosis before onset of somatic mutation.

Lebecque S, de Bouteiller O, Arpin C, Banchereau J, Liu YJ - J. Exp. Med. (1997)

Bottom Line: They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture.The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones.Unmutated sIgM+IgD-CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
B lymphocytes undergo affinity maturation of their antigen receptors within germinal centers. These anatomical structures develop in secondary lymphoid organs from the clonal expansion of a few antigen-specific founder B cells, whose isolation and characterization are reported here. Human germinal center founder cells express the naive B cell markers surface IgM and IgD as well as the germinal center B cell markers CD10 and CD38. They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture. The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones. Unmutated sIgM+IgD-CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.

Show MeSH

Related in: MedlinePlus

Identification of  IgM+IgD+ and IgM+IgD− B  cells within GC: Double anti– IgD (red) and anti–IgM (blue)  staining of a tonsil section. (A)  shows a secondary lymphoid follicle that contains purple  IgD+IgM+ follicular mantle B  cells. Within the GC, IgM immune complexes (blue) on follicular dendritic cells can be observed. In addition, scattered  purple IgM+IgD+ B cells and  blue IgM+IgD− B cells can be  found (×100). (B) Shows a part  of this GC at ×200 magnification.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196025&req=5

Figure 4: Identification of IgM+IgD+ and IgM+IgD− B cells within GC: Double anti– IgD (red) and anti–IgM (blue) staining of a tonsil section. (A) shows a secondary lymphoid follicle that contains purple IgD+IgM+ follicular mantle B cells. Within the GC, IgM immune complexes (blue) on follicular dendritic cells can be observed. In addition, scattered purple IgM+IgD+ B cells and blue IgM+IgD− B cells can be found (×100). (B) Shows a part of this GC at ×200 magnification.

Mentions: It has been previously reported that a small proportion of human GC contain IgD+ B cells (29, 30). Indeed, by double immunohistological staining, we have recently confirmed these observations and further shown that IgD+ B cells within GC display CD38, the majority of them expressing the proliferation associated nuclear antigen Ki67 (28). To distinguish IgM+IgD+CD38+ GC founder cells from highly mutated IgM−IgD+CD38+ GC B cells in situ (26), double staining with anti-IgM and anti-IgD were performed on tonsil sections. While numerous large IgM−IgD+ B blasts were found to be packed within occasional GC dark zones (26), only scattered IgM+IgD+ B cells were found throughout a few GCs (Fig. 4).


Germinal center founder cells display propensity for apoptosis before onset of somatic mutation.

Lebecque S, de Bouteiller O, Arpin C, Banchereau J, Liu YJ - J. Exp. Med. (1997)

Identification of  IgM+IgD+ and IgM+IgD− B  cells within GC: Double anti– IgD (red) and anti–IgM (blue)  staining of a tonsil section. (A)  shows a secondary lymphoid follicle that contains purple  IgD+IgM+ follicular mantle B  cells. Within the GC, IgM immune complexes (blue) on follicular dendritic cells can be observed. In addition, scattered  purple IgM+IgD+ B cells and  blue IgM+IgD− B cells can be  found (×100). (B) Shows a part  of this GC at ×200 magnification.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196025&req=5

Figure 4: Identification of IgM+IgD+ and IgM+IgD− B cells within GC: Double anti– IgD (red) and anti–IgM (blue) staining of a tonsil section. (A) shows a secondary lymphoid follicle that contains purple IgD+IgM+ follicular mantle B cells. Within the GC, IgM immune complexes (blue) on follicular dendritic cells can be observed. In addition, scattered purple IgM+IgD+ B cells and blue IgM+IgD− B cells can be found (×100). (B) Shows a part of this GC at ×200 magnification.
Mentions: It has been previously reported that a small proportion of human GC contain IgD+ B cells (29, 30). Indeed, by double immunohistological staining, we have recently confirmed these observations and further shown that IgD+ B cells within GC display CD38, the majority of them expressing the proliferation associated nuclear antigen Ki67 (28). To distinguish IgM+IgD+CD38+ GC founder cells from highly mutated IgM−IgD+CD38+ GC B cells in situ (26), double staining with anti-IgM and anti-IgD were performed on tonsil sections. While numerous large IgM−IgD+ B blasts were found to be packed within occasional GC dark zones (26), only scattered IgM+IgD+ B cells were found throughout a few GCs (Fig. 4).

Bottom Line: They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture.The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones.Unmutated sIgM+IgD-CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
B lymphocytes undergo affinity maturation of their antigen receptors within germinal centers. These anatomical structures develop in secondary lymphoid organs from the clonal expansion of a few antigen-specific founder B cells, whose isolation and characterization are reported here. Human germinal center founder cells express the naive B cell markers surface IgM and IgD as well as the germinal center B cell markers CD10 and CD38. They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture. The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones. Unmutated sIgM+IgD-CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.

Show MeSH
Related in: MedlinePlus