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Autoreactivity by design: innate B and T lymphocytes

Nature Reviews Immunology volume 1, pages 177–186 (2001)Cite this article

Key Points

  • Innate lymphocytes are a subset of T and B lymphocytes that express a restricted set of semi-invariant, germ-line-encoded, autoreactive antigen receptors.

  • Some innate B-cell and T-cell receptors are genetically favoured during the neonatal period, whereas others are constantly generated over lifetime.

  • Innate lymphocytes consist of 10–50% of the total lymphocyte count and include most B-1 B cells, γδ T cells and CD1d-restricted natural killer T (NKT) cells and a fraction of marginal zone B cells.

  • Innate lymphocytes express an activated effector phenotype in the absence of exogenous immunization and their autoreactivity is controlled by SHP-1 (Src-homology-2-domain-containing protein tyrosine phosphatase 1)-associated inhibitory receptors, such as NK receptors and CD5.

  • Innate lymphocytes represent an evolutionary strategy of immune recognition, which is distinct from adaptive lymphocytes and similar to NK cells, and target conserved self-antigens associated with tissue damage and the various forms of cell stress, injury and death.

  • Innate lymphocytes regulate various autoimmune, infectious and tumour conditions.

  • Innate lymphocytes acquire their peculiar differentiation and tissue-homing properties during development, as a consequence of the high avidity of their germ-line-encoded antigen receptor for self-antigen.

Abstract

Innate B and T lymphocytes are a subset of lymphocytes that express a restricted set of semi-invariant, germ-line-encoded, autoreactive antigen receptors. Although they have long been set apart from mainstream immunological thought, they now seem to represent a distinct immune-recognition strategy that targets conserved stress-induced self-structures, rather than variable foreign antigens. Innate lymphocytes regulate a range of infectious, tumour and autoimmune conditions. New studies have shed light on the principles and mechanisms that drive their unique development and function, and show their resemblance to another subset of innate lymphocytes, the natural killer cells.

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Figure 1: Balancing autoreactive antigen receptors with inhibitory receptors.
Figure 2: Specificity for self-antigen governs differentiation and tissue location of innate lymphocytes.
Figure 3: Borderline avidity to self-antigen drives lineage differentiation.

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Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, 08544, New Jersey, USA

    Albert Bendelac

  2. INSERM U463, Institut de Biologie, Nantes, France

    Marc Bonneville

  3. Department of Microbiology, Tumor Institute, University of Alabama at Birmingham, Birmingham, 35294, Alabama, USA

    John F. Kearney

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DATABASES

LocusLink

apolipoprotein E

CD1c

CD1d

CD5

CD19

CD21

CD22

CD94

IFN-γ

IL-4

IL-15

KGF

MICA

MICB

motheaten

SHP-1

T10

terminal deoxytransferase

Thy-1

OMIM

IDDM

FURTHER INFORMATION

Albert Bendelac's lab

John Kearney's lab

Glossary

IDIOTYPE

A unique feature of an immunoglobulin molecule that is recognized by an anti-idiotypic antibody. In the case of T15, the idiotype is constituted by the canonical sequence of the antigen-binding site.

COMPLEMENTARITY-DETERMINING REGION

(CDR). The most variable parts of immunoglobulin and the T-cell receptor, which forms loops that make contact with specific ligands. There are three such regions (CDR1, CDR2 and CDR3) in each V domain.

N-DIVERSIFICATION

Untemplated nucleotide additions introducing new amino acids at V-D-J junctions.

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Bendelac, A., Bonneville, M. & Kearney, J. Autoreactivity by design: innate B and T lymphocytes. Nat Rev Immunol 1, 177–186 (2001). https://doi.org/10.1038/35105052

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