Address for correspondence: Jean-Pierre de Villartay, INSERM U429, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France. Voice: (33) 01 44 49 50 81; fax: (33) 01 42 73 06 40.
devillar{at}infobiogen.fr
Ann. N.Y. Acad. Sci. 987: 150-157 (2003).
V(D)J recombination constitutes a critical checkpoint in the
development of the immune system as shown in several animal
models as well as severe combined immune deficiency (SCID) condition
in humans. We recently cloned the
Artemis gene, whose mutations
are responsible for RS-SCID, a condition characterized by an
absence of both B and T lymphocytes and associated with increased
sensitivity to ionizing radiations.
Artemis is ubiquitously
expressed and is localized in the nucleus. Artemis belongs to
the metallo-ß-lactamase superfamily and defines a
new group, ß-CASP, within this family. ß-CASP
proteins are ß-lactamases acting on nucleic acids.
While RS-SCID patients harbor
Artemis loss-of-function mutations,
we identified four patients with a combined immunodeficiency
characterized by a low but detectable number of both B and T
lymphocytes caused by hypomorphic mutations in the
Artemis gene.
Two of these patients developed aggressive B cell lymphomas,
a condition that suggests Artemis may be considered a "caretaker"
factor, similarly to the other V(D)J recombination/DNA repair
actors.
