Introduction and Overview of Lymphoid Neoplasms

Question 1

What cells make up the

innate immune system ?

Answer 1

• NK cells
• NK-like cells (CD3 and CD56 +)
• Gamma delta T cells

They are important in mucosal and cutaneous defences

They do not encounter antigens and the MHC molecules so do not need APC cells.

Question 2

What is the definition of

naive B cells ?

Answer 2

• often CD5 positive
• small resting lymphocytes that circulate in the PB and also occupy primary lymphoid follicles and follicle mantle zones

Question 3

What neoplasm arises from bone marrow

precursor B cells ?

Answer 3

• B lymphoblastic leukemia/lymphoma
• the precursors seen in the BM include:
  
  • Progenitor B cells
  • Pre-B cell
  • Immature B cell

Question 4

What neoplasms arise from

cells in the interfollicular area of

peripheral lymphoid tissue ?

Answer 4

• Mantle cell lymphoma
  
  • pre-GC lymphoma
• Cells included in normal interfollicular areas:
  
  • Naive B cells
  • Extrafollicular B blast
  • short-lived plasma cell

Question 5

What lymphomas arise from the germinal

center cells ?

Answer 5

• Follicular lymphoma
• Burkitt lymphoma
• DLBCL (some)
• Hodgkin Lymphoma

Question 6

What neoplasms arise from the post

GC cells?

Answer 6

• Marginal zone, MALT lymphomas
• LPL
• CLL/SLL
• DLBCL (some)
• Plasma cell myeloma
• Post GC cells include:
  
  • long lived plasma cells
  • memory B cells (marginal zone)

Question 7

What cells normally express

IRF4/MUM1?

Answer 7

• late centrocytes and plasma cells
• centrocytes after interaction with FDCs and antigens turn of BCL6 and differentiate into memory B cells and plasma cells
  
  • expression of BCL6 and MUM1 are opposite

Question 8

What is the normal role of MYC

in B cell maturation ?

Answer 8

• MYC is upregulated upon interaction of naive B cells with antigen and T cells by the action of BCL6
• MYC is essential for germinal center formation
• In normal reactive lymph nodes MYC highlights a population of centrocytes in the light zone of the germinal center.
  
  • it is repressed in the dark zone

Note: BCL6 gets switched off by centrocytes when they differentiate into memory B cells or plasma cells

Question 9

Where can post-germinal center B

cells be found in the body ?

Answer 9

• these are memory B cells
• they circulate in the:
  
  • PB
  • some are found in marginal zones of lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT)
• Marginal zone B cells usually express pan B cell antigens with IgM (only low levels of IgD)
  
  • they are negative for CD5 and CD10

Note: plasma cells home to the bone marrow

Question 10

What are the markers typically seen on

post-germinal center plasma cells ?

Answer 10

• IgG or IgA cytoplasmic immunoglobulins
• lack surface Ig and CD20
• positive for IRF4, CD79a, CD38 and CD138

IMP: both memory B cells and plasma cells have mutated IGV genes but no do not continue to undergo mutation

Question 11

What is the immunoprofile of cortical thymocytes ?

Answer 11

• immature T cell phenotype
  
  • (+) TdT, CD1a, CD3, CD5, and CD7
  • CD3 is first expressed in the cytoplasm prior to complete T cell gene rearrangement and export to the cell membrane
  • double negative for CD4 and CD8

Note: T lymphocytes develop in the bone marrow and then move to the thymus to undergo maturation

Question 12

What is known about medullary thymocytes ?

Answer 12

• similar immunophenotype to mature T cells
• there are 2 classes of T cells
  
  • alpha beta
  • gamma delta
  • distinction is based no structure of the T cell receptor
  • both are associated with the CD3 complex, which contains gamma, delta and epsilon chains

Question 13

How are NK cells different ?

Answer 13

• they do not have a complete T cell receptor complex
  
  • only express the epsilon and zeta chains of CD3 in their cytoplasm
• positive for:
  
  • CD2, CD7 and sometimes CD8 but surface CD3 is negative
  • CD16 and CD56 with variable expression of CD57
• they have cytoplasmic cytotoxic granules

Question 14

How do NK cells kill their targets ?

Answer 14

• they kill them through an antibody-mediated cell toxicity mechanism
• OR
  
  • mechanism that involves the killer cell immunoglobulin like receptors (KIRS)

Question 15

What neoplasms arise from the innate

lymphoid cells ?

Answer 15

• aggressive NK cell leukemia
• systemic EBV positive T cell lymphoma of childhood
• hepatosplenic gamma delta T cell lymphoma
• gamma delta T cell lymphoma arising in mucosal sites

Question 16

What is the immunophenotype of gamma delta cells ?

Answer 16

• lack expression of CD4, CD8 and CD5
• account for <5% of all normal T cells
• they have a restricted distribution
  
  • found mainly in splenic red pulp, intestinal epithelium, and other epithelial sites
• first line of defense against bacterial peptides and major component against immunity against mycobacteria and mucosal infections

Question 17

What are the T cells of the adaptive immune system ?

Answer 17

• heterogeneous and very complex system
• Naive T cells
• Effector T cells
  
  • regulatory and cytotoxic
• Memory T cells

Note: T cell lymphomas of the adaptive immune system primarily occur in adults and are mainly nodal. Innate lymphomas tend to be in younger people and extranodal.

Question 18

What do we know about CD4+ T cells?

Answer 18

• these are primarily regulatory and act via cytokine production
• they are divided into 2 groups
  
  • T helper 1
    
    • secrete IL2 and interferon gamma but not IL4, IL5 or IL6
    • provide help mainly to other T cells and macrophages
  • T helper 2
    
    • secrete IL4, IL5, IL6, and IL10
    • help B cells and are key to antibody production

IMP: CD4 + T cells can act both to help and to suppress immune responses and consist of multiple subpopulations

Question 19

What is the purpose of T regulatory cells?

Answer 19

• they have many functions including suppressing the immune response to cancer and limiting inflammatory responses in tissues
  
  • thought to prevent autoimmunity
• CD4+ T cells
• Immunophenotype expression:
  
  • CD25
  • FOXP3
  • CD4
• ATLL has been linked to T regulatory cells
  
  • has associated with marked immunosuppression

Question 20

What are the T helper 17 cells?

Answer 20

• they are a recently identified subset of CD4+ effector T cells
• they express IL17
• important role in immune-mediated inflammtory diseases and in other conditions

Question 21

What are T follicular helper cells?

Answer 21

• they are a CD4+ subset of T cells
• they are found in normal germinal centers
• they provide assistance to B cells in the germinal center reactions
• Unique immunophenotype:
  
  • BCL6 and CD10
  • CD4, CD57, PD1 and CXCL13
• Note: CXCL13
  
  • causes induction and proliferation of follicular dendritic cells
  • facilitates migration of B and T cells expressing CXCR5 in the germinal centers

Question 22

What is the role of CXCL13 ?

Answer 22

• causes induction and proliferation of follicular dendritic cells
• also facilitates the migration of B cells and T cells expressing CXCR5 into the germinal center

Question 23

What are two neoplasms with a T follicular helper cell immunophenotype ?

Answer 23

• AITL
• Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder

Question 24

What T cells are antigen independent ?

Answer 24

• prothymocyte
• subcapsular thymocyte
• cortical thymocytes
• medullary thymocytes

Question 25

What are the antigen dependent T cells ?

Answer 25

• Peripheral T cell
• Follicular T helper cell
• T-regulatory cell
• TH1
• TH2
• TH17