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B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals.

Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, Lamers MC, Carsetti R - J. Exp. Med. (1999)

Bottom Line: They develop into the transitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen.Mice with genetic deletions of elements participating in the B cell receptor signaling cascade display developmental arrest at the T1 or T2 stage.The analysis of these defects showed that the development of T2 and mature B cells from T1 precursors requires defined qualitative and quantitative signals derived from the B cell receptor and that the induction of longevity and maturation requires different signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Immunology, University of Freiburg, Germany.

ABSTRACT
Only mature B lymphocytes can enter the lymphoid follicles of spleen and lymph nodes and thus efficiently participate in the immune response. Mature, long-lived B lymphocytes derive from short-lived precursors generated in the bone marrow. We show that selection into the mature pool is an active process and takes place in the spleen. Two populations of splenic B cells were identified as precursors for mature B cells. Transitional B cells of type 1 (T1) are recent immigrants from the bone marrow. They develop into the transitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen. Mature B cells can be generated from T1 or T2 B cells. Mice with genetic deletions of elements participating in the B cell receptor signaling cascade display developmental arrest at the T1 or T2 stage. The analysis of these defects showed that the development of T2 and mature B cells from T1 precursors requires defined qualitative and quantitative signals derived from the B cell receptor and that the induction of longevity and maturation requires different signals.

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T2 B cells are in the primary follicle of normal mice. (A) Sections of normal spleen were fixed and stained with TRITC-labeled goat anti–mouse IgM and FITC-labeled anti-mouse IgD. Green and red fluorescence were measured separately by confocal laser microscopy, and the pictures obtained were then overlaid (magnification 100). M, mature B cells. (B) The sector indicated by the square in A was scanned with a 250-fold amplification to better visualize single cells. T1 B cells (red) are indicated by the single-headed arrow and T2 (yellow) by the double-headed arrow. Mature B cells are green.
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Figure 4: T2 B cells are in the primary follicle of normal mice. (A) Sections of normal spleen were fixed and stained with TRITC-labeled goat anti–mouse IgM and FITC-labeled anti-mouse IgD. Green and red fluorescence were measured separately by confocal laser microscopy, and the pictures obtained were then overlaid (magnification 100). M, mature B cells. (B) The sector indicated by the square in A was scanned with a 250-fold amplification to better visualize single cells. T1 B cells (red) are indicated by the single-headed arrow and T2 (yellow) by the double-headed arrow. Mature B cells are green.

Mentions: To study the localization of T1, T2, and mature B cells in the spleens of normal mice, we stained sections with TRITC-coupled Abs to IgM and with FITC-coupled Abs to IgD (Fig. 4 A). IgMbrightIgD− MZ and T1 B cells appear in red, T2 B cells, which coexpress high amounts of IgM and IgD, appear in yellow, and mature B cells, which are bright for IgD and have downregulated IgM, are green (Fig. 4). T1 B cells are in the outer periarteriolar lymphoid sheet (PALS) close to the primary follicle. T2 and mature B cells are together inside the follicle. Mature B cells can also be seen in the outer PALS and in the red pulp. MZ B cells, as expected, surround the follicle. Fig. 4 B shows an enlargement of the bordering area between outer PALS and follicle, where single T1 (red; indicated by the single-headed arrow) and T2 cells (yellow; indicated by the double-headed arrow) can be seen, together with mature B cells (bright green).


B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals.

Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, Lamers MC, Carsetti R - J. Exp. Med. (1999)

T2 B cells are in the primary follicle of normal mice. (A) Sections of normal spleen were fixed and stained with TRITC-labeled goat anti–mouse IgM and FITC-labeled anti-mouse IgD. Green and red fluorescence were measured separately by confocal laser microscopy, and the pictures obtained were then overlaid (magnification 100). M, mature B cells. (B) The sector indicated by the square in A was scanned with a 250-fold amplification to better visualize single cells. T1 B cells (red) are indicated by the single-headed arrow and T2 (yellow) by the double-headed arrow. Mature B cells are green.
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Related In: Results  -  Collection

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Figure 4: T2 B cells are in the primary follicle of normal mice. (A) Sections of normal spleen were fixed and stained with TRITC-labeled goat anti–mouse IgM and FITC-labeled anti-mouse IgD. Green and red fluorescence were measured separately by confocal laser microscopy, and the pictures obtained were then overlaid (magnification 100). M, mature B cells. (B) The sector indicated by the square in A was scanned with a 250-fold amplification to better visualize single cells. T1 B cells (red) are indicated by the single-headed arrow and T2 (yellow) by the double-headed arrow. Mature B cells are green.
Mentions: To study the localization of T1, T2, and mature B cells in the spleens of normal mice, we stained sections with TRITC-coupled Abs to IgM and with FITC-coupled Abs to IgD (Fig. 4 A). IgMbrightIgD− MZ and T1 B cells appear in red, T2 B cells, which coexpress high amounts of IgM and IgD, appear in yellow, and mature B cells, which are bright for IgD and have downregulated IgM, are green (Fig. 4). T1 B cells are in the outer periarteriolar lymphoid sheet (PALS) close to the primary follicle. T2 and mature B cells are together inside the follicle. Mature B cells can also be seen in the outer PALS and in the red pulp. MZ B cells, as expected, surround the follicle. Fig. 4 B shows an enlargement of the bordering area between outer PALS and follicle, where single T1 (red; indicated by the single-headed arrow) and T2 cells (yellow; indicated by the double-headed arrow) can be seen, together with mature B cells (bright green).

Bottom Line: They develop into the transitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen.Mice with genetic deletions of elements participating in the B cell receptor signaling cascade display developmental arrest at the T1 or T2 stage.The analysis of these defects showed that the development of T2 and mature B cells from T1 precursors requires defined qualitative and quantitative signals derived from the B cell receptor and that the induction of longevity and maturation requires different signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Immunology, University of Freiburg, Germany.

ABSTRACT
Only mature B lymphocytes can enter the lymphoid follicles of spleen and lymph nodes and thus efficiently participate in the immune response. Mature, long-lived B lymphocytes derive from short-lived precursors generated in the bone marrow. We show that selection into the mature pool is an active process and takes place in the spleen. Two populations of splenic B cells were identified as precursors for mature B cells. Transitional B cells of type 1 (T1) are recent immigrants from the bone marrow. They develop into the transitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen. Mature B cells can be generated from T1 or T2 B cells. Mice with genetic deletions of elements participating in the B cell receptor signaling cascade display developmental arrest at the T1 or T2 stage. The analysis of these defects showed that the development of T2 and mature B cells from T1 precursors requires defined qualitative and quantitative signals derived from the B cell receptor and that the induction of longevity and maturation requires different signals.

Show MeSH