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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.


The IgM response to immunization with a T-independent antigen is enhanced in Cd244-/- mice.WT (closed symbol) and Cd244-/- (open symbol) mice were immunized (i.p.) with the T-independent antigen NP-ficoll (30 μg). Blood was collected on days 0, 7 and 14, and NP-specific IgM (top graph) and IgG3 (bottom graph) titers were determined by ELISA. The O.D. value for NP-specific IgM at the 1:800 dilution and NP-specific IgG3 at the 1:100 dilution are shown. Data shown are the mean ± SE of 8 mice. *p<0.05; **p<0.001; ***p<0.0001
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pone.0137314.g006: The IgM response to immunization with a T-independent antigen is enhanced in Cd244-/- mice.WT (closed symbol) and Cd244-/- (open symbol) mice were immunized (i.p.) with the T-independent antigen NP-ficoll (30 μg). Blood was collected on days 0, 7 and 14, and NP-specific IgM (top graph) and IgG3 (bottom graph) titers were determined by ELISA. The O.D. value for NP-specific IgM at the 1:800 dilution and NP-specific IgG3 at the 1:100 dilution are shown. Data shown are the mean ± SE of 8 mice. *p<0.05; **p<0.001; ***p<0.0001

Mentions: Given the specific role for B1b cells in T-independent immune responses [30, 31], we next asked whether their increase in Cd244-/- mice would augment the B cell response to the T-independent antigen NP-ficoll. In T-independent immune responses, ligation of the BCR with a repeating antigen such as NP-ficoll induces BCR signaling that is sufficient to drive the production of antigen-specific Ig without the requirement for T cell help in the germinal center [32]. Following immunization with NP-ficoll, we measured serum NP-specific Ig on days 0, 7 and 14. As expected, levels of NP-specific IgM peaked on day 7 in WT mice that had begun to wane on day 14 (Fig 3A). In Cd244-/- mice, levels of NP-specific IgM were sustained on day 14 resulting in a significant increase in their serum levels (Fig 6A). Because T-independent immune responses lead to isotype class switching to IgG3, we also measured NP-specific IgG3 and found that it was significantly elevated on both day 7 and 14 in Cd244-/- mice (Fig 3B). Given that very little isotype-class switched IgG3 is generated following immunization with T-independent antigens the O.D. values are low. Even though the error bars are relatively small for the IgG3 data (Fig 6B), caution needs to be used to avoid overinterpretation of the data.


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)

The IgM response to immunization with a T-independent antigen is enhanced in Cd244-/- mice.WT (closed symbol) and Cd244-/- (open symbol) mice were immunized (i.p.) with the T-independent antigen NP-ficoll (30 μg). Blood was collected on days 0, 7 and 14, and NP-specific IgM (top graph) and IgG3 (bottom graph) titers were determined by ELISA. The O.D. value for NP-specific IgM at the 1:800 dilution and NP-specific IgG3 at the 1:100 dilution are shown. Data shown are the mean ± SE of 8 mice. *p<0.05; **p<0.001; ***p<0.0001
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getmorefigures.php?uid=PMC4554987&req=5

pone.0137314.g006: The IgM response to immunization with a T-independent antigen is enhanced in Cd244-/- mice.WT (closed symbol) and Cd244-/- (open symbol) mice were immunized (i.p.) with the T-independent antigen NP-ficoll (30 μg). Blood was collected on days 0, 7 and 14, and NP-specific IgM (top graph) and IgG3 (bottom graph) titers were determined by ELISA. The O.D. value for NP-specific IgM at the 1:800 dilution and NP-specific IgG3 at the 1:100 dilution are shown. Data shown are the mean ± SE of 8 mice. *p<0.05; **p<0.001; ***p<0.0001
Mentions: Given the specific role for B1b cells in T-independent immune responses [30, 31], we next asked whether their increase in Cd244-/- mice would augment the B cell response to the T-independent antigen NP-ficoll. In T-independent immune responses, ligation of the BCR with a repeating antigen such as NP-ficoll induces BCR signaling that is sufficient to drive the production of antigen-specific Ig without the requirement for T cell help in the germinal center [32]. Following immunization with NP-ficoll, we measured serum NP-specific Ig on days 0, 7 and 14. As expected, levels of NP-specific IgM peaked on day 7 in WT mice that had begun to wane on day 14 (Fig 3A). In Cd244-/- mice, levels of NP-specific IgM were sustained on day 14 resulting in a significant increase in their serum levels (Fig 6A). Because T-independent immune responses lead to isotype class switching to IgG3, we also measured NP-specific IgG3 and found that it was significantly elevated on both day 7 and 14 in Cd244-/- mice (Fig 3B). Given that very little isotype-class switched IgG3 is generated following immunization with T-independent antigens the O.D. values are low. Even though the error bars are relatively small for the IgG3 data (Fig 6B), caution needs to be used to avoid overinterpretation of the data.

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.