Learn: B Cell Development and Activation

Where does B-cell development begin?

Bone marrow

What do committed lymphoid progenitors give rise to?

B cells

What are B cells called during the early stage of B-cell development?

Pro-B cells

What major gene rearrangement begins during the Pro-B-cell stage?

Immunoglobulin heavy-chain VDJ recombination

What immunoglobulin/BCR is expressed by immature B cells?

IgM

True or False: B cells complete their maturation outside the bone marrow.

True

Where do B cells complete their maturation?

Spleen

What types of proteins are expressed by bone marrow stromal cells?

Cytokines, cell-surface ligands, chemokines

What is the role of stromal cells in B-cell development?

They support survival, differentiation, and development.

Is interaction between precursor B cells and stromal cells required for B-cell development?

Yes

What is one of the earliest molecular events involving hematopoietic stem cells (HSCs)?

HSCs express c-Kit (CD117), which binds stem cell factor (SCF) from bone marrow stromal cells.

What proteins are expressed by hematopoietic stem cells?

c-Kit (CD117), Sca-1

What does c-Kit bind?

Stem cell factor (SCF)

What important transcription factors are expressed by early progenitor cells?

Ikaros, PU.1, E2A

What genes begin being expressed as developing lymphoid cells prepare for immunoglobulin rearrangement?

RAG1, RAG2, TdT

What transcription factors are involved in further B-cell commitment?

EBF1 and PAX5

At what B-cell stage does immunoglobulin heavy-chain rearrangement begin?

Pro-B stage

What is the overall sequence of early lymphocyte/B-cell commitment?

HSC → early progenitor → lymphoid commitment → B-cell commitment

What are the stages of B-cell development in the bone marrow?

HSC → MPP → ELP → CLP → Pre-Pro-B → Pro-B → Pre-B → Immature B cell

What happens after the immature B cell leaves the bone marrow?

Immature B → Blood → Spleen → T1 → T2 → Mature B cell

How do immature B cells leave the bone marrow and enter the blood?

They respond to S1P in the blood through S1P receptors, then travel to the spleen.

What is negative selection in the bone marrow?

It eliminates or modifies self-reactive immature B cells.

What is negative selection in the spleen?

T1 transitional B cells that recognize self-antigen with sufficiently high affinity can undergo negative selection and elimination.

What is BCR/receptor editing?

A self-reactive immature B cell reactivates RAG genes and undergoes additional light-chain gene rearrangement.

What is the purpose of central selection during B-cell development?

To prevent strongly self-reactive immature B cells from continuing normal development.

What are developing B cells called in the spleen?

T1 and T2 transitional B cells

What are mature B cells in the spleen called in the guide?

Follicular B2 cells

What developmental features do B and T cells share?

Both originate from hematopoietic stem cells, are lymphocytes of adaptive immunity, and undergo antigen-receptor gene rearrangement.

What are the two major types of B-cell responses?

T-cell dependent and T-cell independent

What does a T-cell-dependent B-cell response require?

A helper T cell

Does a T-cell-independent response require helper T cells?

No

What is Signal 1 during T-cell-dependent B-cell activation?

The B cell binds antigen through its BCR/immunoglobulin receptor.

What happens after BCR engagement?

ITAM tyrosines on Igα and Igβ are phosphorylated by Src-family kinases.

What is Signal 2 during T-cell-dependent B-cell activation?

Costimulatory interaction, including CD40 on the B cell binding CD40L on the helper T cell.

Is CD40-CD40L Signal 1 or Signal 2?

Signal 2

According to the guide, which additional molecules participate in B-cell/T-cell interaction?

B cell: CD40 and B7; Helper T cell: CD40L and CD28

What is Signal 3 in T-cell-dependent B-cell activation?

T-cell-derived cytokines

What happens to B cells when they do not encounter/bind antigen?

They recirculate through secondary lymphoid tissues while depending on survival signals.

What is the role of BAFF?

BAFF is important for mature B-cell survival.

What happens to mature B cells that cannot obtain sufficient BAFF?

They undergo apoptosis.

What approximate half-life does the study guide give for recirculating B cells?

4.5 months

Can a T-cell-dependent B-cell response work in the absence of the thymus?

No

What combination was required for the antibody response described in the guide?

Both bone marrow-derived cells AND thymus-derived cells.

Can a T-cell-dependent B-cell response work well without bone marrow-derived cells?

No

True or False: Naïve B cells encounter antigens in lymph nodes and the spleen.

True

What surface immunoglobulin does a naïve B cell have?

IgM

Do naïve B cells secrete antibodies?

No

What is a plasmablast?

An antibody-secreting B-lineage cell that secretes antibodies, can still proliferate, and still has BCR.

Can plasmablasts still divide?

Yes

Can plasma cells divide?

No

How much surface immunoglobulin do plasma cells have?

Little or none

What is the main function of plasma cells?

Rapid secretion of large amounts of antibody

Which cells are referred to as antibody-forming/antibody-secreting cells?

Plasmablasts and plasma cells

Which cytokines does the study guide list as being involved in isotype switching?

IL-4, IL-10, IL-13, IL-15, IL-21, IFN-α, IFN-β, TGF-β

True or False: Plasmablasts and plasma cells that pass through germinal centers can enter circulation and take up residence in bone marrow niches.

True

Which cells are listed near plasma-cell niches in the bone marrow?

Eosinophils, megakaryocytes, stromal cells

What survival pathway is associated with eosinophils and megakaryocytes in the guide?

APRIL → BCMA

What pathway is associated with stromal cells?

CXCL12 → CXCR4

What are the two major forms of T-independent B-cell activation?

TI-1 and TI-2

What is the example given for a TI-1 antigen?

LPS

What receptor does LPS interact with in the TI-1 example?

TLR4, along with membrane immunoglobulin/BCR signaling.

What is the basic idea of TI-1 activation?

Signaling occurs through both receptors described in the guide.

Which molecules are listed for TI-2 B-cell activation?

CD21, C3d, membrane immunoglobulin

Which proteins are listed on naïve B cells?

CD19, CD20, IgD

Which proteins are listed on memory B cells?

CD19, CD20, CD27

Which proteins are listed on plasma cells?

CD27HI, CD38HI, CD138 +/−

Which cells have surface immunoglobulin according to the comparison?

Naïve B cells and memory B cells

Which cells have MHC class II according to the comparison?

Naïve B cells and memory B cells

Which cell performs high-rate immunoglobulin secretion?

Plasma cell

Do naïve or memory B cells show high-rate immunoglobulin secretion in the guide's table?

No