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Localization and Differential Expression of Activation-Induced Cytidine Deaminase in the Amphibian Xenopus upon Antigen Stimulation and during Early Development¹

Shauna Marr^2,*, Heidi Morales^2,*, Andrea Bottaro^*,, Michelle Cooper, Martin Flajnik and Jacques Robert^2,*

^* Department of Microbiology and Immunology, and Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642; and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201

As in mammals, B cell maturation in the amphibian Xenopus involves somatic hypermutation (SHM) and class switch recombination to diversify the B cell receptor repertoire in response to Ag stimulation. Unlike mammals, however, the resulting increase in Ab affinity is poor in Xenopus, which is possibly related to the absence of germinal centers and a suboptimal selection mechanism of SHM. In mammals, both SHM and class switch recombination are mediated by the activation-induced cytidine deaminase enzyme and under Ag-dependent regulation. Given its evolutionary conservation in jawed vertebrates, we used activation-induced cytidine deaminase as a marker to monitor and localize B cell maturation in Xenopus upon immune responses and during early development. In adult, Xenopus laevis AID (XlAID) was detected mainly in the spleen, where cells expressing XlAID were preferentially distributed in follicular B cell zones, although some XlAID⁺ cells were also found in the red pulp. XlAID was markedly up-regulated in the spleen with different kinetics upon bacterial stimulation and viral infection. However, during secondary anti-viral response XlAID was also noticeably expressed by PBLs, suggesting that XlAID remains active in a subset of circulating B cells. During ontogeny, XlAID expression was detected as early as 5 days postfertilization in liver before the first fully differentiated B cells appear. Concomitant with appearance of mature B cells XlAID was up-regulated upon bacterial stimulation or viral infection at later larval stages. This study highlights the conserved involvement of XlAID during Ag-dependent B cell responses in Xenopus but also suggests another role in B cell differentiation earlier in ontogeny.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by National Institutes of Health R25-GM64133 (to S.M.), National Institutes of Health R24-AI-059830 (to J.R.) and NSF MCB-0136536 (to J.R. and H.M.), National Institutes of Health AI45012 (to A.B.), and National Institutes of Health RR06603 (to M.F.).

² S.M. and H.M. are equally contributing authors.

³ Address correspondence and reprint requests to Dr. Jacques Robert, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642. E-mail address: robert{at}mail.rochester.edu

⁴ Abbreviations used in this paper: GC, germinal center; SHM, somatic hymermutation; AID, activation-induced cytidine deaminase; CSR, class-switch recombination; APBS, amphibian PBS; PFA, paraformaldehyde.