Development of B lymphocytes

2 populations of B cells

B-1 cells & B-2 cells

Beginning of B cell development in birds

Hematopoietic stem cells migrate to bursa of fabricus

First stage of B cell development

Antigen-independent

Where does antigen-independent development occur?

In primary lymphoid organ

Second stage of B cell development

Antigen-dependent

Where does antigen-dependent development occur?

In secondary lymphoid organ

Process of antigen-independent development

Stem cell -- pre-B cell -- immature B cell -- mature B cell

Process of antigen-dependent development

Immunoglobulin activated by antigen and will develop into IgM or undergo isotype switching & somatic mutations to develop into IgG, IgA, IgE, or memory B cells

Immature B cells undergo selection to become…

self-tolerant

If an immature B cell binds to multivalent self-antigen, it is given a signal to…

Die via apoptosis

If an immature B cell binds to soluble self-antigen, it is given a signal to…

Migrates to periphery and become an anergic B cell

If an immature B cell undergoes no self-reaction, it is given a signal to…

Become a mature B cell

B cells have to interact with ______ to get survival signals and leave lymphocyte

follicular dendritic cells

2 types of antigens for B cell stimulation

1. Thymus dependent (TD) antigens

2. Thymus independent (TI) antigens

Thymus dependent antigens

Needs T cell help for activating B cell and production of antibodies

Typical structure of TD antigens

Proteins or glycoproteins

TI antigens

Can induce antibody production in the absence of T cell help

Typical structure of TI antigens

Bacterial capsular polysaccharides with highly repetitive structures or B-cell mitogens (ex: LPS)

TD antigen action

Presents antigen to T cell in order to proliferate and secrete IgM

Germinal center

Center of proliferating B cells surrounding by helper T cells

TI antigen action

Does not require T cells, directly activated by antigen, secretes only IgM (no proliferation)

How long does IgM survive?

~5 days

How long do isotype switched antibodies survive?

months to years

Primary immune response

Period of adaptive immunity activation and antibody development

Primary immune response is characterized by…

low affinity antibodies (IgM) and low intensity antibody production

Secondary immune response is characterized by…

high affinity antibodies (isotype switching) & more intense production

Secondary immune response

Occurs after secondary exposure

Lag after initial exposure before primary immune response

Usually 5-10 days (longer)

Lag after secondary exposure before secondary immune response

Usually 1-3 days (shorter)

What occurs after a patient’s first vaccine?

Primary immune response

What occurs after a patient’s vaccine booster?

Secondary immune response

Polyclonal antibodies

Purified from serum of immunized animals with multiple specificities and affinities

Monoclonal antibodies

Produced in vitro by immortalized plasma cells with single specificity and affinity and unlimited supply of identical antibody molecules

Typical origin of polyclonal antibodies

Goats or rabbits

Typical origin of monoclonal antibodies

Mice

Creation of monoclonal antibodies

1. B cell fused with myeloma cells

2. Form hybridomas

3. Select for specific hybridoma cells for cloning

Clinical applications of monoclonal antibodies

• Diagnostic tests

• Diagnostic imaging

• Therapeutic applications

Therapeutic applications of monoclonal antibodies

• Cancer

• Cardiovascular diseases

• Inflammatory diseases

• Transplant rejection

• Pain management

• Allergy

• Infectious diseases