HIGHLIGHTSIN BRIEF

B-CELL RESPONSESAIDing diversity
Of humans, frogs, sharks and chickens, which is the odd one out? If you
are interested in B cells, the answer ischickens — the first three animals use
somatic hypermutation to diversify
the variable (V) regions of theirrearranged antibody genes, whereas
chickens, together with pigs and rabbits, use gene conversion. Two groups
have now shown that a putative RNA
editing enzyme — activationinduced cytidine deaminase (AID)— essential for somatic hypermutation and immunoglobulin classswitch recombination is also requiredfor gene conversion.
It is unclear why some species use
somatic hypermutation and others
use gene conversion. The processes
are very different — somatic hypermutation involves the introductionof untemplated single base-pairalterations, whereas in gene conversion, new sequences are copied fromnearby pseudogenes. However, it has
been shown recently that when geneconversion is blocked in a chicken
B-cell line, somatic hypermutation
can occur instead, indicating that thetwo processes might be linked mechanistically.
The two new studies made use ofthe chicken B-cell line DT40, which
undergoes gene conversion spontaneously. Hiroshi Arakawa and colleagues, reporting in Science, used avariant of this cell line with aframeshift mutation in its rearranged
V segment that does not, therefore,
express surface immunoglobulin(IgM). Gene conversion can repair
the mutation, leading to the expression of surface IgM. The rate ofreversion provides a quick

VAC C I N E S

and easy measure of gene conversion.
AID was knocked out by gene targeting to create AID−/− DT40 cells.
Subclones were expanded for 18 days
then analysed for surface IgM expression. The reversion rate in AID−/− cells
was reduced by at least 100-fold, andsequencing confirmed that this wasdue to an absence of gene conversion.
Reuben Harris and colleagues also
generated AID−/− cells, but in an IgM+
DT40 cell line. The cells wereexpanded for 40 days, then IgMlow
cells were sorted and their V genes
sequenced. None of the 89 AID−/−cells analysed had undergone geneconversion, whereas gene-conversion
events were detected in more than
one-third of the AID+/+ cells.
These studies promote AID to theposition of master controller of antibody gene modifications. The mechanisms of somatic hypermutation,
gene conversion and class-switch
recombination are unknown; however, it has been proposed that DNA
breaks (double- or single-stranded)might be pivotal to all three processes.
Harris et al. conclude by predicting,“itis likely that AID is involved in the formation of an initiating DNA lesioncommon to switch recombination,
hypermutation and gene conversion”.
Jennifer Bell
References and links
ORIGINAL RESEARCH PAPERS Arakawa, H.,

Hauschild, J. & Buerstedde, J. M. Requirement of
the activation-induced deaminase (AID) gene for
immunoglobulin gene conversion. Science 295,1301–1306 (2002) | Harris, R. S. et al.
Immunoglobulin V gene conversion in a cultured
B-cell line is dependent upon AID. Curr. Biol. 2002
February 11 (DOI 10.1016/S0960982202007170).

Adaptive immune response of Vγ2Vδ2+ T cells during
mycobacterial infections.
Shen, Y. et al. Science 295, 2255–2258 (2002)

Correlates of protection for tuberculosis in humans remain
poorly characterized, and the role of Vγ2Vδ2+ T cells — the major
human γδ T-cell population — is not well documented. Shen et al.
show that Vγ2Vδ2+ T cells in macaques proliferate in response toimmunization with BCG. BCG-vaccinated macaques developed
protective immunity against a fatal form of tuberculosis, whichcoincided with the expansion of alveolar Vγ2Vδ2+ T-cellpopulations. So, Vγ2Vδ2+ T cells can develop memory responses
and vaccines that target Vγ2Vδ2+ T cells might be useful.
VAC C I N E S

Efficient delivery of peptides to APC by use ofMHC-class-II-specific troy-bodies.
Lunde, E. et al. J. Immunol. 168, 2154–2162 (2002)

Generating robust T-cell responses remains a challenge for
vaccine development. Here, MHC-class-II-specific antibodies
were engineered to contain peptide epitopes from various model
antigens within their constant regions. These ‘troy-bodies’ wereshown to target the peptide to antigen-presenting cells, including
B cells, macrophages and dendritic cells. In vivo, specific T-cell
activation was 1,000–10,000-fold greater with troy-bodies thanwith native protein or peptide alone.
A U TO I M M U N I T Y

Attenuated experimental autoimmune
encephalomyelitis in Eta-1/ostepontin-deficient mice.
Jansson, M. et al. J. Exp. Med. 168, 2096–2099 (2002)

T-helper 1 (TH1) responses have been implicated in thepathogenesis of multiple sclerosis (MS). Jansson et al. investigated
the role of the TH1-promoting cytokine Eta-1 in the developmentof experimental autoimmune encephalomyelitis (EAE), an
animal model of MS. Eta-1−/− and wild-type mice were equallysusceptible to the induction of EAE. However, Eta-1−/− micedeveloped less severe pathology, had diminished Th1 responses
and recovered quicker than wild-type mice.
T- C E L L D E V E LO P M E N T

Role for CCR7 ligands in the emigration of newly
generated T lymphocytes from neonatal thymus.
Ueno, T. et al. Immunity 16, 205–218 (2002)

The developmental stages through which T cells pass in the thymus
are well defined, but it is unclear what controls the emigration ofT cells from the thymus. Previous studies have implicatedchemokine signals in this process. By adding chemokines to fetal
thymic organ cultures, and analysing thymic emigration in micethat are deficient or neutralized for certain chemokines and/orchemokine receptors, the authors highlight the importance of a
CCL19- and CCR7-dependent pathway of thymic emigration.

NATURE REVIEWS | IMMUNOLOGYVOLUME 2 | APRIL 2002 | 2 2 3