• Molecules and Cells
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• v.19 no.3
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• pp.445-451
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• 2005

Activation-induced cytidine deaminase (AID) is needed for Ig class switch recombination (CSR). We explored the effect of LPS on the expression of AID during B cell differentiation, and the role of AID in IgA isotype expression. In normal spleen B cells, LPS increased AID transcription up to 48 h post-stimulation, i.e. around the time of Ig CSR. TGF-${\beta}1$ and AID were required for IgA expression, and LPS contributed to $TGF{\beta}1$-induced IgA production largely by inducing AID. Interestingly, LPS repressed AID transcription in $sIgA^+$ B cells but still stimulated IgA production mainly by increasing the rate of IgA secretion. Our data indicate that LPS contributes to $TGF{\beta}1$-induced IgA isotype expression in at least two ways: by stimulating AID transcription before CSR and by enhancing the IgA secretion rate after CSR.

• IMMUNE NETWORK
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• v.12 no.1
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• pp.27-32
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• 2012

Background: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-${\beta}1$-induced germ line transcript ${\alpha}$ ($GLT{\alpha}$) and IL-4-induced $GLT{\gamma}1$ as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.215-220
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• 2005

Background: Transforming growth factor-${\beta}$ (TGF-${\beta}1$) directs class switch recombination (CSR) to IgA isotype, which is a predominant antibody in mucosal surfaces. Although IgA is preferentially committed in mucosal lymphoid tissues, it is not definitely established whether hallmarks of IgA CSR such as IgA germ-line transcripts (GLT ${\alpha}$), post-switch transcripts (PST ${\alpha}$) and circle transcripts (CT ${\alpha}$) are readily expressed in such tissues. Therefore, we compared the expression of these transcripts among mouse Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen. Methods: Levels of GLTs, PSTs and CTs were measured by RT-PCR in isolated PPs, MLNs and spleen cells. Results: GLT ${\alpha}$ and PST ${\alpha}$ were well expressed in PP and MLN cells but in spleen cells. Similar patterns were observed in the expression of GL ${\gamma}$2b and PST ${\gamma}$2b. On the other hand, these transcripts were only inducible in spleen cells upon stimulated with LPS and TGF-${\beta}1$. In addition, CT${\alpha}$ and CT${\gamma}$2b were detected in PP cells. Conclusion: PP B cells readily express IgA GLT, PST, and CT. Overall expression patterns of these transcripts were similar in MLN cells. Thus, these results suggest that microenvironment of PP and MLN influences spontaneous IgA CSR, which lacks in systemic lymphoid tissues such as spleen.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.196-202
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• 2011

Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.230-239
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• 2012

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.