T lymphocyte dependence of the antibody response to 'T lymphocyte independent type 2' antigens.

Abstract

With regard to their capacity for antibody induction, antigens can be classified as either T lymphocyte dependent (TD) or as T lymphocyte independent (TI).1 In the immune response to TD antigens, T lymphocyte help to B lymphocytes is essential for the regulation of B lymphocyte proliferation, production of immunoglobulins, immunoglobulin class switching, rescue of B lymphocytes from apoptotic death, germinal centre formation, and generation of B lymphocyte memory.2 In contrast to TD antigens, TI antigens induce antibody production without the help of T lymphocytes. TI antigens can be further divided into TI type 1 antigens (TI-1), which are polyclonal B lymphocyte activators (e.g. lipopolysaccharides), and TI type 2 (TI-2) antigens. TI-2 antigens are able to directly stimulate B lymphocytes. However, the antibody response to TI-2 antigens is somehow influenced by T lymphocytes.3 TI-2 antigens do not induce immunological memory and antibodies to TI-2 antigens in humans only develop after the age of 2 years.4,5 Generally, TI-2 antigens are antigens that consist of repetitive biochemical structures such as polymeric protein antigens, trinitrophenyl-ficoll (TNP-ficoll), and dinitrophenyl-ficoll (DNP-ficoll). A clinically important group among the TI-2 antigens are the bacterial capsular polysaccharides.6 Capsular polysaccharides of Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are responsible for the bacterial virulence and antibodies to capsular polysaccharides provide protection against invasive infections with these bacteria.7 The delay in antibody formation to encapsulated bacteria renders infants and young children highly susceptible to infections with encapsulated bacteria, especially from the ages of 4 to 6 months on, when the placentally derived maternal IgG is metabolized.5 Therefore, children younger than 2 years of age are more at risk for invasive infections caused by encapsulated micro-organisms.8 Children with a persisting defect in the production of antibodies specific for pneumococcal capsular antigens after this age have the so-called ‘specific antibody deficiency with normal immunoglobulins’ (SADNI). They suffer from recurrent pneumococcal infections, although their immunoglobulin and immunoglobulin subclass levels and responses to protein antigens are normal.9–12 It is estimated that 5–10% of the children referred for evaluation of recurrent infections have SADNI and it is therefore highly important to understand the immunological background of the antibody formation against TI-2 antigens.13 In this review we will summarize the current understanding of how T lymphocytes modulate the antibody response against TI-2 antigens.