T he B lymphocytes that bind protein antigens by their membrane Ig antigen receptors endocytose these antigens, process them in endosomal vesicles, and display class II MHC–associated peptides for recognition by CD4+ helper T cells (Fig. 1). The membrane Ig of B cells is a high-affinity receptor that enables a B cell to specifically bind a particular antigen, even when the extracellular concentration of the antigen is very low. In addition, antigen bound by membrane Ig is endocytosed efficiently and is delivered to late endosomal vesicles and lysosomes, where proteins are processed into peptides that bind to class II MHC molecules . Therefore, B lymphocytes are efficient APCs for the antigens they specifically recognize.

Fig1. Antigen presentation by B lymphocytes to helper T cells. B cells specific for a protein antigen bind and internalize that antigen, process it, and present peptides attached to class II major histocompatibility complex (MHC) molecules to helper T cells. The B cells and helper T cells are specific for the same antigen, but the B cells recognize native (conformational) epi topes, and the helper T cells recognize peptide fragments of the antigen bound to class II MHC molecules.

Any one B cell may bind a conformational epitope of a native protein antigen, internalize and process the protein, and display multiple peptides from that protein for T cell recognition. Therefore, B cells recognize one epitope of a protein antigen first, and helper T cells recognize different epitopes of the same protein later. Because B cells efficiently internalize and process the antigen for which they have specific receptors, and helper T cells recognize peptides derived from the same antigen, the ensuing interaction remains antigen specific. B cells are capable of activating previously differentiated effector T cells but are inefficient at initiating the responses of naive T cells.

The idea that a B cell recognizes one epitope of an intact antigen and displays different epitopes (peptides) for recognition by helper T cells was first demonstrated by studies using hapten-carrier conjugates. A hapten is a small chemical that is recognized by B cells but stimulates strong antibody responses only if it is attached to a carrier protein. In this situation, the B cell binds the hap ten portion, ingests the conjugate, and displays peptides derived from the carrier to helper T cells. The antibody response is, of course, specific for the epitope that the B cell recognized (the hapten in this example), and the peptides derived from the carrier protein simply bring helper T cells into the reaction. This concept has been exploited to develop effective vaccines against microbial polysaccharides (Fig. 2). Some bacteria have polysaccharide-rich capsules, and the polysaccharides themselves stimulate T-independent antibody responses, which are weak in infants and young children. If the polysaccharide is coupled to a carrier protein, however, effective T-dependent responses are induced against the polysaccharide because helper T cells specific for the carrier are engaged in the response. In this situation, the B cell recognizes the polysaccharide (equivalent to the hapten) and the T cell recognizes peptides from the attached protein (the carrier); the antibody response is specific for the polysaccharide, but it is much stronger than conventional T-independent responses because helper T cells are “forced” to participate. Such conjugate vaccines have been very useful for inducing protective immunity against bacteria such as Haemophilus influenzae, especially in infants, and current vaccines against pneumococcus are also conjugate vaccines. 

Fig2. The principle of conjugate vaccines: the hapten-carrier concept. In order to generate strong antibody responses against a microbial polysaccharide, the polysaccharide is coupled to a protein (in this case, tetanus toxoid). B cells that recognize the polysaccharide ingest it and present peptides from the protein to helper T cells, which stimulate the polysaccharide-specific B cells. Thus isotype switching, affinity maturation, and long-lived plasma cells and memory cells (all features of responses to proteins) are induced in a response to polysaccharides. (Note that some B cells will also recognize the tetanus toxoid and antibodies will be produced against the carrier protein, but this has no bearing on the antipolysaccharide response.) Ig, Immunoglobulin.