Limits...
2B4 Is Dispensable for T-Dependent B Cell Immune Responses, but Its Deficiency Leads to Enhanced T-Independent Responses Due to an Increase in Peritoneal Cavity B1b Cells.

Ray A, Yuan CY, Miller NM, Mei H, Dittel BN - PLoS ONE (2015)

Bottom Line: We found that the splenic cellularity in Cd244-/- mice was significantly reduced due to a reduction in both CD4 T cells and follicular (Fo) B cells; whereas, the number of peritoneal cavity B cells was increased.When we evaluated T-independent immune responses, we found that antigen-specific IgM and IgG3 were elevated in the serum following immunization.These data indicate that 2B4 dampens T-independent B cell responses due to a reduction in peritoneal cavity B cells, but has minimal impact on T-dependent B cell responses.

View Article: PubMed Central - PubMed

Affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.

ABSTRACT
The signaling lymphocyte activation molecule (SLAM) family plays important roles in adaptive immune responses. Herein, we evaluated whether the SLAM family member 2B4 (CD244) plays a role in immune cell development, homeostasis and antibody responses. We found that the splenic cellularity in Cd244-/- mice was significantly reduced due to a reduction in both CD4 T cells and follicular (Fo) B cells; whereas, the number of peritoneal cavity B cells was increased. These findings led us to examine whether 2B4 modulates B cell immune responses. When we examined T-dependent B cell responses, while there was no difference in the kinetics or magnitude of the antigen-specific IgM and IgG1 antibody response there was a reduction in bone marrow (BM) memory, but not plasma cells in Cd244-/- mice. When we evaluated T-independent immune responses, we found that antigen-specific IgM and IgG3 were elevated in the serum following immunization. These data indicate that 2B4 dampens T-independent B cell responses due to a reduction in peritoneal cavity B cells, but has minimal impact on T-dependent B cell responses.

No MeSH data available.


Total B cell numbers are reduced in the spleen of Cd244-/- mice due to a reduction in Fo B cells.A representative splenic B cell gating strategy is shown (A). The absolute number of B cells (B220+) (B) and that of the Fo (B220+IgMintCD21intCD23+CD93-) (C), MZ (B220+IgMhiCD21hiCD23-) (D), T1 (B220+IgMhiCD21loCD23-CD93+) (E), T2 (B220+IgMhiCD21loCD23+CD93+) (F), T3 (B220+IgMintCD21intCD23+CD93+) (G) and T2-MZP (B220+IgMhiCD21hiCD23+) (H) B cell subsets in the spleen of WT and Cd244-/- mice was determined by flow cytometry. Data are shown as the mean ± SE of four mice. *p<0.05; **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4554987&req=5

pone.0137314.g002: Total B cell numbers are reduced in the spleen of Cd244-/- mice due to a reduction in Fo B cells.A representative splenic B cell gating strategy is shown (A). The absolute number of B cells (B220+) (B) and that of the Fo (B220+IgMintCD21intCD23+CD93-) (C), MZ (B220+IgMhiCD21hiCD23-) (D), T1 (B220+IgMhiCD21loCD23-CD93+) (E), T2 (B220+IgMhiCD21loCD23+CD93+) (F), T3 (B220+IgMintCD21intCD23+CD93+) (G) and T2-MZP (B220+IgMhiCD21hiCD23+) (H) B cell subsets in the spleen of WT and Cd244-/- mice was determined by flow cytometry. Data are shown as the mean ± SE of four mice. *p<0.05; **p<0.01.

Mentions: We determined whether the absence of 2B4 altered B cell differentiation in the spleen using a gating strategy to identify the Fo and MZ splenic mature B cells populations as well as their transitional (T) 1, T2 and T3 precursors (Fig 2A) [16]. We also analyzed the T2-MZ precursor (P), which is the immediate precursor to the MZ lineage (Fig 2A) [17]. When we quantitated total B cells, we found that the reduction in splenic cellularity in Cd244-/- mice was also due to a significant reduction in the number of B220+ B cells (Fig 2B). By quantitating the mature splenic B cell subsets we found that Fo (Fig 2C), but not MZ (Fig 2D), B cell numbers were significantly reduced. We next asked whether the reduction in Fo B cells was due to altered differentiation into the Fo lineage and found no difference in the transitional (T) 1 (Fig 2E) or T2 (Fig 2F) precursor populations between WT and Cd244-/- mice. We also found no difference in the T3 (Fig 2G) or T2-MZP (Fig 2F) subsets. These data indicate that the homeostasis of Fo B cells is uniquely altered by a global deletion in 2B4.


2B4 Is Dispensable for T-Dependent B Cell Immune Responses, but Its Deficiency Leads to Enhanced T-Independent Responses Due to an Increase in Peritoneal Cavity B1b Cells.

Ray A, Yuan CY, Miller NM, Mei H, Dittel BN - PLoS ONE (2015)

Total B cell numbers are reduced in the spleen of Cd244-/- mice due to a reduction in Fo B cells.A representative splenic B cell gating strategy is shown (A). The absolute number of B cells (B220+) (B) and that of the Fo (B220+IgMintCD21intCD23+CD93-) (C), MZ (B220+IgMhiCD21hiCD23-) (D), T1 (B220+IgMhiCD21loCD23-CD93+) (E), T2 (B220+IgMhiCD21loCD23+CD93+) (F), T3 (B220+IgMintCD21intCD23+CD93+) (G) and T2-MZP (B220+IgMhiCD21hiCD23+) (H) B cell subsets in the spleen of WT and Cd244-/- mice was determined by flow cytometry. Data are shown as the mean ± SE of four mice. *p<0.05; **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554987&req=5

pone.0137314.g002: Total B cell numbers are reduced in the spleen of Cd244-/- mice due to a reduction in Fo B cells.A representative splenic B cell gating strategy is shown (A). The absolute number of B cells (B220+) (B) and that of the Fo (B220+IgMintCD21intCD23+CD93-) (C), MZ (B220+IgMhiCD21hiCD23-) (D), T1 (B220+IgMhiCD21loCD23-CD93+) (E), T2 (B220+IgMhiCD21loCD23+CD93+) (F), T3 (B220+IgMintCD21intCD23+CD93+) (G) and T2-MZP (B220+IgMhiCD21hiCD23+) (H) B cell subsets in the spleen of WT and Cd244-/- mice was determined by flow cytometry. Data are shown as the mean ± SE of four mice. *p<0.05; **p<0.01.
Mentions: We determined whether the absence of 2B4 altered B cell differentiation in the spleen using a gating strategy to identify the Fo and MZ splenic mature B cells populations as well as their transitional (T) 1, T2 and T3 precursors (Fig 2A) [16]. We also analyzed the T2-MZ precursor (P), which is the immediate precursor to the MZ lineage (Fig 2A) [17]. When we quantitated total B cells, we found that the reduction in splenic cellularity in Cd244-/- mice was also due to a significant reduction in the number of B220+ B cells (Fig 2B). By quantitating the mature splenic B cell subsets we found that Fo (Fig 2C), but not MZ (Fig 2D), B cell numbers were significantly reduced. We next asked whether the reduction in Fo B cells was due to altered differentiation into the Fo lineage and found no difference in the transitional (T) 1 (Fig 2E) or T2 (Fig 2F) precursor populations between WT and Cd244-/- mice. We also found no difference in the T3 (Fig 2G) or T2-MZP (Fig 2F) subsets. These data indicate that the homeostasis of Fo B cells is uniquely altered by a global deletion in 2B4.

Bottom Line: We found that the splenic cellularity in Cd244-/- mice was significantly reduced due to a reduction in both CD4 T cells and follicular (Fo) B cells; whereas, the number of peritoneal cavity B cells was increased.When we evaluated T-independent immune responses, we found that antigen-specific IgM and IgG3 were elevated in the serum following immunization.These data indicate that 2B4 dampens T-independent B cell responses due to a reduction in peritoneal cavity B cells, but has minimal impact on T-dependent B cell responses.

View Article: PubMed Central - PubMed

Affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.

ABSTRACT
The signaling lymphocyte activation molecule (SLAM) family plays important roles in adaptive immune responses. Herein, we evaluated whether the SLAM family member 2B4 (CD244) plays a role in immune cell development, homeostasis and antibody responses. We found that the splenic cellularity in Cd244-/- mice was significantly reduced due to a reduction in both CD4 T cells and follicular (Fo) B cells; whereas, the number of peritoneal cavity B cells was increased. These findings led us to examine whether 2B4 modulates B cell immune responses. When we examined T-dependent B cell responses, while there was no difference in the kinetics or magnitude of the antigen-specific IgM and IgG1 antibody response there was a reduction in bone marrow (BM) memory, but not plasma cells in Cd244-/- mice. When we evaluated T-independent immune responses, we found that antigen-specific IgM and IgG3 were elevated in the serum following immunization. These data indicate that 2B4 dampens T-independent B cell responses due to a reduction in peritoneal cavity B cells, but has minimal impact on T-dependent B cell responses.

No MeSH data available.