Sistema de kanban tradicional

(CR2) that binds the receptor for the C3d component of complement. CD21 also hinds CD23 (Aubry et al., 1992) and is the receptor for EBV

(Matsumoto et al., 1993). TAPA-1 is a tetra-span-transmembrane protein

that is expressed in many cell types and can associate with MHC class 11

(Angelisova et al., 1994; Schick and Levy, 1993). Leu-13 coprecipitates

with CD 19 in some B cell lines but not all and is not an essential part of

the complex (Matsumoto et al., 1993). The ligand for CD 19 has not been

identified but artificial ligation via monoclonal antibodies to CD 19 have

found that stim ulating B cells through CD 19 can have both costimulatory

and inhibitory effects. Crosshnking CD 19 and the BCR costimulates B

cells and induces proliferation (Carter and Fearon, 1992). This

32

complexes binding to the BCR and CD21 and thereby reducing the

threshold for B cell activation and proliferation (Matsumoto et al., 1993).

However, if ligated independently of the BCR, CD 19 can inhibit B cell

proliferation and activation but not BCR expression (Rigley and Callard,

1991; Callard et al., 1992).

1,3.2 P r o lif e r a tio n a n d a c ti v a t i o n o f B c e lls by T c e ll in d e p e n d e n t m e c h a n is m s

Some antigens such as polysaccharides are capable of eliciting a B cell

response in the absence of direct T ceU help. These T independent (TI)

antigens may be subdivided into type 1 or type 2 antigens according to

their ability to give antibody responses in X id mice. Their properties are summarised in table l.l.(M ond et al., 1995).

Table 1.1. C haracteristics o f T cell dependent and T cell

Tl-1 TI-2 TD

prototype antigen B. abortus capsular polysaccharides proteins

T cells required no no yes

T cell regulation no yes yes

Onset of

responsiveness

early late early

Induction of memory no no yes

isotyi) e/idiotyp e restriction

TI antigens capable of inducing a B cell antibody response in X id (CBA/N)

mice are classed as TI type 1 (TI-1) and those that do not as TI type 2 (TI-

2). Xid mice have mutations in the btk gene and are unable to signal efficiently through sIgM. TI-2 antigens appear to act by crosshnking

surface immunoglobuhn. Furthermore, mice with deletions in the

cytoplasmic domain of the inb-l gene fail to respond to TI-2 type antigens again suggesting stimulation through the BCR is required for the

response. Although, TI-2 antigens do not require T cells the response may

be regulated by T cells in mice and man (Braley MuUen, 1974; Baker, 1992, Kalthoff et al., 1991; Hoon et al., 1991; Griffioen et al., 1992).

Response to TI-2 antigens (unhke both TI-1 and TD antigens) occurs late

in human development at about 2 years of age and coincides with the

formation of the mantle zone in lymphnodes (Mond et al., 1995).

TI-1 type are typically bacterial polysaccharides, polymeric proteins, and

hpopolysaccharide antigens. At high concentrations, TI-1 antigens are

polyclonal B cell activators and mitogens but act independently of the

BCR. It is hkely that during normal infections the iri vivo concentrations of TI-1 antigens are low, and only antigen-specific B ceUs are hkely to be

activated.

1,3,3 T a n d B c ell c o lla b o r a tio n in T d e p e n d e n t r e s p o n s e s

Antibody responses to most proteins depends on cohaboration between B

34

On leaving the bone marrow, mature naive B cells circulate through the

periphery and pass through secondary lymphoid organs where they meet

antigen (MacLennan, 1994b). Antigen bound by the B cell is internalised,

processed and re-expressed in association with class II and presented to T

cells via MHC class II. The subsequent cell surface interactions between B

and T cells involves a number of different molecules as shown in figure 1.4

and are described below.

CD40/CD40L

CD40 is a type 1 integral membrane protein belonging to the TNFR

superfamily (Banchereau et al., 1994a). It is expressed on a wide variety of

cell types but plays a central role in B cell differentiation. Ligating CD40

promotes B cell proliferation (Fanslow et al., 1992; Saeland et al., 1993;

Armitage et al., 1993; Splawski et al., 1993; Renard et al., 1994), rescues B

cells from apoptosis (Valentine and Licciardi, 1992; Parry et al., 1994) and

promotes immunoglobulin class switching (Gascan et al., 1991; Fanslow et

al., 1992; Armitage et al., 1993; Jumper et al., 1994; Galibert et al., 1994).

The ligand for CD40 (CD40L) is expressed on activated but not resting T

cells and the interaction between CD40 and CD40L provides an important

signal(s) for T cell B cell collaboration. In humans, mutations in the

CD40L gene results in the immunodeficiency disease X-hnked hyper IgM

B c e l l C D 5 8 C D 2 0 C D 1 1 a / 1 8 C D 4 0 T c e l l C D 2

s urf ace IgM

C D 2 2