Did Germinal Centers Evolve Under Differential Effects of Diversity vs Affinity? - Artificial Immune Systems - page 1

Did Germinal Centers Evolve Under Differential
Effects of Diversity vs Anity?

Jose Faro 1 , 2 , Jaime Combadao 1 ,andIsabelGordo 1

1 Estudos Avancados de Oeiras, Instituto Gulbenkian de Ciencia, Apartado 14,
2781-901 Oeiras, Portugal
[e-mail], [e-mail],
[e-mail]
2 Universidade de Vigo, Edificio de Ciencias Experimentais,
Campus As Lagoas-Marcosende, 36310 Vigo, Spain
[e-mail]

Abstract. The classical view on the process of mutation and a nity
maturation that occurs in GCs assumes that their major role is to gen-
erate high anity levels of serum Abs, as well as a dominant pool of high
anity memory B cells, through a very ecient selection process. Here
we present a model that considers different types of structures where a
mutation selection process occurs, with the aim at discussing the evolu-
tion of Germinal Center reactions. Based on the results of this model, we
suggest that in addition to anity maturation, the diversity generated
during the GC reaction may have also been important in the evolution to-
wards the presently observed highly organized structure of GC in higher
vertebrates.

1 Introduction

Vertebrates have evolved a complex immune system (IS) that e ciently con-
tributes to protect them from many infectious and toxic agents. To cope with
such large variety of agents the IS generates a large diversity of lymphocyte re-
ceptors. This occurs through various mechanisms activated during lymphocyte
development. The first one consists in the random recombination of relatively
few gene segments into a full variable (V) region gene of immunoglobulins(Ig)
heavy and light chains, allowing the formation of many different receptors [1].
In higher vertebrates (birds, mammals) the relevance of this mechanism for di-
versity generation in the primary B-cell repertoire varies with different species,
being followed in some of them by other mechanisms like V-region gene conver-
sion or somatic hypermutation (SHM) that act on rearranged V-region genes [2].
This initial repertoire is submitted to selection before B cells reach full maturity,
thus getting purged of overt self-reactivity [1].
During an immune response to a protein antigen (Ag) the SHM mechanism
is triggered in some of the responding, mature B cells. Most mutations are dele-
terious (decrease the antibody (Ab) anity for Ag) or neutral, but a few may
increase the anity [3]. This is followed by an increase of serum anity starting