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Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen.

Song H, Cerny J - J. Exp. Med. (2003)

Bottom Line: However, MZ B cells were also capable of forming germinal centers (GCs) albeit with a delay, compared with FO B cells.Surprisingly, the MZ but not the FO memory response included IgM Ab.We conclude that MZ B cells are heterogeneous, comprising cells for both early AFC response and GC/memory pathway against TD antigens.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201-1559, USA.

ABSTRACT
Marginal zone (MZ) B cells play a major role in the first-line responses against blood-born T-independent bacterial antigens (TI), but the full scope of their immune functions is not known. Here we compare the responses of MZ and follicular (FO) B cells to a T-dependent antigen (TD), hapten-(4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken gamma-globulin, in a cell transfer system. Consistent with the conventional paradigm, MZ B cells but not FO B cells rapidly generated the early burst of NP-specific antibody-forming cells (AFC), high levels of IgM Ab, and early IgG with relatively high affinity to NP. However, MZ B cells were also capable of forming germinal centers (GCs) albeit with a delay, compared with FO B cells. The early AFCs and the GCs originated from different MZ precursors, but the MZ- and FO-derived GCs were similar in VH gene repertoire, somatic mutation, and production of late AFC and IgG Ab. Surprisingly, the MZ but not the FO memory response included IgM Ab. We conclude that MZ B cells are heterogeneous, comprising cells for both early AFC response and GC/memory pathway against TD antigens.

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Kinetics of IgM (a) and IgG (b) serum Ab responses after single injection of 40 μg of NP-CGG/alum in mice reconstituted with purified MZ B cells (MZ, filled symbols), FO B cells (FO, open symbols), and whole splenic B cells (+ and ×) plus TH cells. Each symbol represents one animal. Two independent experiments are shown using circles (• and ○), triangles (▴ and Δ) and different crosses (+ and ×). The points below the horizontal line represent negative sera (titer <1:10).
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fig5: Kinetics of IgM (a) and IgG (b) serum Ab responses after single injection of 40 μg of NP-CGG/alum in mice reconstituted with purified MZ B cells (MZ, filled symbols), FO B cells (FO, open symbols), and whole splenic B cells (+ and ×) plus TH cells. Each symbol represents one animal. Two independent experiments are shown using circles (• and ○), triangles (▴ and Δ) and different crosses (+ and ×). The points below the horizontal line represent negative sera (titer <1:10).

Mentions: Consistent with the pattern of cellular responses in single-reconstituted animals, the MZ mice mounted a robust NP-specific IgM serum Ab response during the first week after the immunization (Fig. 5 a) and switched to IgG Ab on day 8 (Fig. 5 b). FO mice did not produce any detectable serum Ab until day 8; the level of IgM was 10-fold lower than in the MZ mice, whereas the IgG titers had a similar range among individual mice in both groups. Thus, the massive, early AFC formation in the MZ mice correlates well with the anti-NP IgM response. The origin of serum Ab in FO mice can be either from the dispersed plasmacytes (Fig. 2 f) or perhaps from B cells in the follicles, which might have secreted Ig without differentiation into typical plasmacytes. Interestingly, the MZ mice maintained 10-fold higher IgM Ab titers throughout the entire 2-mo period of observation, and as described below, they also displayed a brisk, recall IgM Ab response to the Ag boost. Each of the two independent experiments shown in Fig. 5 included groups of control mice reconstituted either with whole unseparated splenic B cell population together with purified TH, or with TH alone, and immunized with NP-CGG. Notably, mice with unseparated B cells maintained intermediate levels of IgM Ab relative to the MZ and FO mice, confirming that MZ B cells, which represent 5–10% of spleen B cells, make the major contribution to IgM responses. None of the mice from the control group reconstituted with only T cells produced detectable anti-NP serum Ab, demonstrating that neither a contaminating donor B cell population nor “leaky” host B cells contributed to the anti-NP responses (not depicted).


Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen.

Song H, Cerny J - J. Exp. Med. (2003)

Kinetics of IgM (a) and IgG (b) serum Ab responses after single injection of 40 μg of NP-CGG/alum in mice reconstituted with purified MZ B cells (MZ, filled symbols), FO B cells (FO, open symbols), and whole splenic B cells (+ and ×) plus TH cells. Each symbol represents one animal. Two independent experiments are shown using circles (• and ○), triangles (▴ and Δ) and different crosses (+ and ×). The points below the horizontal line represent negative sera (titer <1:10).
© Copyright Policy
Related In: Results  -  Collection

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fig5: Kinetics of IgM (a) and IgG (b) serum Ab responses after single injection of 40 μg of NP-CGG/alum in mice reconstituted with purified MZ B cells (MZ, filled symbols), FO B cells (FO, open symbols), and whole splenic B cells (+ and ×) plus TH cells. Each symbol represents one animal. Two independent experiments are shown using circles (• and ○), triangles (▴ and Δ) and different crosses (+ and ×). The points below the horizontal line represent negative sera (titer <1:10).
Mentions: Consistent with the pattern of cellular responses in single-reconstituted animals, the MZ mice mounted a robust NP-specific IgM serum Ab response during the first week after the immunization (Fig. 5 a) and switched to IgG Ab on day 8 (Fig. 5 b). FO mice did not produce any detectable serum Ab until day 8; the level of IgM was 10-fold lower than in the MZ mice, whereas the IgG titers had a similar range among individual mice in both groups. Thus, the massive, early AFC formation in the MZ mice correlates well with the anti-NP IgM response. The origin of serum Ab in FO mice can be either from the dispersed plasmacytes (Fig. 2 f) or perhaps from B cells in the follicles, which might have secreted Ig without differentiation into typical plasmacytes. Interestingly, the MZ mice maintained 10-fold higher IgM Ab titers throughout the entire 2-mo period of observation, and as described below, they also displayed a brisk, recall IgM Ab response to the Ag boost. Each of the two independent experiments shown in Fig. 5 included groups of control mice reconstituted either with whole unseparated splenic B cell population together with purified TH, or with TH alone, and immunized with NP-CGG. Notably, mice with unseparated B cells maintained intermediate levels of IgM Ab relative to the MZ and FO mice, confirming that MZ B cells, which represent 5–10% of spleen B cells, make the major contribution to IgM responses. None of the mice from the control group reconstituted with only T cells produced detectable anti-NP serum Ab, demonstrating that neither a contaminating donor B cell population nor “leaky” host B cells contributed to the anti-NP responses (not depicted).

Bottom Line: However, MZ B cells were also capable of forming germinal centers (GCs) albeit with a delay, compared with FO B cells.Surprisingly, the MZ but not the FO memory response included IgM Ab.We conclude that MZ B cells are heterogeneous, comprising cells for both early AFC response and GC/memory pathway against TD antigens.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201-1559, USA.

ABSTRACT
Marginal zone (MZ) B cells play a major role in the first-line responses against blood-born T-independent bacterial antigens (TI), but the full scope of their immune functions is not known. Here we compare the responses of MZ and follicular (FO) B cells to a T-dependent antigen (TD), hapten-(4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken gamma-globulin, in a cell transfer system. Consistent with the conventional paradigm, MZ B cells but not FO B cells rapidly generated the early burst of NP-specific antibody-forming cells (AFC), high levels of IgM Ab, and early IgG with relatively high affinity to NP. However, MZ B cells were also capable of forming germinal centers (GCs) albeit with a delay, compared with FO B cells. The early AFCs and the GCs originated from different MZ precursors, but the MZ- and FO-derived GCs were similar in VH gene repertoire, somatic mutation, and production of late AFC and IgG Ab. Surprisingly, the MZ but not the FO memory response included IgM Ab. We conclude that MZ B cells are heterogeneous, comprising cells for both early AFC response and GC/memory pathway against TD antigens.

Show MeSH