Slp

Self-antigen

I reactive

Productive immunoglobulin gene rearrangements l-1 __+ Ag se It-reactive

Mutation and selection in germinal center

Self reactivity or diminished affinity_

Improved affinity

Small pre-BII

Immature B cell

Mature B cell

Developmental stage of a B cell

Figure 1 Mechanisms of central tolerance Central tolerance is established by negative selection which prevents immature self anti-gen-reactive lymphocytes from developing into mature autoreactive T and B cells. The main mechanism of negative selection is apoptosis but developmental arrest, receptor editing and anergy also play a role.

Figure 2 How immature lymphocytes expressing self antigen-specific TCRs or BCRs are prevented from maturation into functionally competent autoreactive T or B cells. This schematic, which purposely ignores the actual data, is intended to illustrate the complexity of intercellular and inter-molecular interactions which are involved in deciding about the fate of immature autoreactive lymphocytes. Better understanding of the molecular mechanisms of central tolerance requires elucidation of the role of the everincreasing number of individual components of Inter- and intracellular communication systems.

DEATH |[~ANERGY || RECEPTOR EDITING || PROLIFERATION 11 DIFFERENTIATION |

DEATH |[~ANERGY || RECEPTOR EDITING || PROLIFERATION 11 DIFFERENTIATION |

Figure 2 How immature lymphocytes expressing self antigen-specific TCRs or BCRs are prevented from maturation into functionally competent autoreactive T or B cells. This schematic, which purposely ignores the actual data, is intended to illustrate the complexity of intercellular and inter-molecular interactions which are involved in deciding about the fate of immature autoreactive lymphocytes. Better understanding of the molecular mechanisms of central tolerance requires elucidation of the role of the everincreasing number of individual components of Inter- and intracellular communication systems.

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