Conventional B cells

The B cells produced in the marrow after the first year of life fall into this category. Three stages of conventional B cell differentiation can be identified:

Table 20.3 Differences between the three

main types of human B cell found in

adults.

B-cell type

Marrow IgM+, IgD-

Recirculating

Marginal zone

Diameter

~8 |M

~10 |m

Chromatin

Condensed

Condensed

Open

Cytoplasm volume/basophilia

Scanty/little

Scanty/little

Moderate/moderate

Proliferating

No

No

No

Lifespan

About 3 days

4 or more weeks

3 or more weeks

Antigen-independent movement

Migrate from marrow to 2°

Migrate between the 2°

Remain in the marginal zones

lymphoid tissue

lymphoid tissues

Surface Ig

IgM

IgM and IgD

IgM or IgG or IgA

Memory or virgin

All virgin

Almost all virgin

Variable mixture of virgin

and memory

Ig V-region mutations

None

Not present

Present in memory cells

Molecules expressed on the cell surface

CD19, 20, 37, 40 and class II MHC

+ve

+ve

+ve

CD21, 39

-ve

+ve

+ve

CD5

-ve

some +ve

-ve

CD23

-ve

+ve

-ve

CD25

-ve

-ve

+ve

CD38

-ve

-ve

-ve

Capacity to respond to different classes of antigen

Bacterial cell wall lipopolysaccharide

+

+

+

Bacterial capsular polysaccharide

-

-

+

Protein-based antigens

+

+

+

IgM+, IgD cells of the marrow are representative of newly produced virgin B cells.

IgM+, IgD cells of the marrow are representative of newly produced virgin B cells.

1 newly produced virgin B cells;

2 recirculating B cells;

3 marginal zone B cells.

These three cell types do not represent different cell lineages, as recirculating cells are derived from newly produced virgin B cells and marginal zone cells mature from recirculating cells. Most newly produced virgin B cells die without becoming recirculating cells, and only some recirculating cells mature to become marginal zone cells. The three types of conventional B cell differ in phenotype (Table 20.3), which reflects marked differences in the signals that influence their survival and induce them to proliferate and differentiate. Recirculation is a process by which cells migrate continually between the follicles of secondary lymphoid tissues via blood and lymph. Most recirculating B cells are virgin cells, whereas the B cells of the marginal zones do not recirculate and are a mixture of virgin and memory cells. In some lymphoid organs that are regularly exposed to antigen, such as the palatine tonsils and Peyer's patches, most marginal zone cells are memory cells.

Newly produced virgin B cells

These cells are produced in the bone marrow in large numbers throughout life and represent the only way the recirculating pool can be replenished, as recirculating B cells do not proliferate unless they are activated by antigen. Antigen-driven proliferation of recirculating cells can generate memory cells, but most of these become marginal zone memory B cells.

If a newly produced virgin B cell encounters self antigen expressed on a cell surface, it may enter apoptosis within the marrow and in this way some, but by no means all, autoreactive B cells are eliminated. Soluble autoantigens binding to the antigen receptor of a newly produced virgin B cell may be taken up and processed, and the resulting peptides are presented on the cell surface in association with MHC molecules (Figure 20.3). These cells become programmed to seek cognate interaction with primed T cells, but die after 3 days without proliferating or secreting antibody if this interaction is not made. As most autoreactive T cells have been eliminated during thymic education, it follows that B-cell tolerance is heavily dependent on

T-cell tolerance. The consequences of a successful interaction between B cells that have taken up antigen and primed T cells are discussed later.

Recirculating B cells

These cells are small, non-dividing virgin B lymphocytes that are classically surface IgM+ and IgD+. They are in a constant state of migration between the follicles of secondary lymphoid organs. On their way to the follicles, they migrate through the T cell-rich zones that contain antigen-presenting cells and have an average lifespan of 4 or more weeks.

Marginal zone B cells

These cells were first identified as a major B-cell population in the spleen, where most of the cells are IgM+, IgD-. Some of these cells express surface IgG or IgA. Almost all of these cells in the tonsils and Peyer's patches have features of memory B cells as they have undergone immunoglobulin class switching and somatic hypermutation of their immunoglobulin variable-region genes.

Marginal zone cells respond to capsular polysaccharides

Marginal zone cells, like recirculating B cells, respond to T cell-dependent antigens and to bacterial cell wall lipopolysaccharides (thymus-independent type 1, TI-1, antigens). Unlike recirculating B cells, they will also respond to bacterial capsular poly-saccharides. Capsular polysaccharides are thymus-independent type 2 (TI-2) antigens. These antigens do not evoke antibody responses until several months after birth, and levels of antibody produced in response to these antigens do not reach adult levels until 5 years of age. Antibodies to the capsular polysaccharides of Streptococcus pneumoniae, Haemophilus influenzae B and Neisseria meningitidis are important in eliminating these pathogens from the body. Infection with these encapsulated bacteria is a particular problem in patients with hypogammaglobulinaemia. They have been estimated to cause some 5 million deaths worldwide per year in infants under 5 years of age, mostly after the first 36 months of life, when antibody transferred from the mother has been lost.

It is quite unclear why immune responses against TI-2 antigens should be delayed for so long during ontogeny, whereas TD and TI-1 responses can occur before birth. It cannot simply be that antibodies against these antigens are harmful in early life, for they are present in the perinatal period as the result of maternal Ig transfer across the placenta. (See Figure 20.12 for responses to conjugate vaccines made up of capsular polysac-charide and an immunogenic protein.)

The majority of peripheral T cells express aP TCR. When these aP T cells leave the thymus, most express either CD4 or CD8 on their surface and are restricted to the recognition of peptides in the context of MHC class II or class I molecules respectively. A minority of T cells express a y8 TCR.

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