Extra

Immunoglobulin light chains

Lght chains form part of the b-cell receptor and may therefore be considered as a pan b-cell marker from late lymphoblasts until plasma cell differentiation. If abnormal cells express predomnantly kappa or lambda then clonality can be inferred. Absence of light chain is also abnormal and may incicate clonality.

normal function and expression

The antigen-recognising structure of the B-cell receptor is the immunoglobulin molecule formed from either kappa or lambda light chains in combination with immunoglobulin heavy chains. Normal mature b cells therefore express surface light chains as part of their B-cell receptor. During pro-B to pre-B cell development immunoglobulin genes rearrange to form unique structures Kappa or lambda light chains appear on the surface of immature B cells at later stages of development remaining expressed until plasma cell development when immunoglobulin is secreted so expression is within cytoplasmic secretory vesicles.

what is its diagnostic role

• acquisition or loss of surface light-chain expression acquisition of surface light chains does not occur until late in b-precursor cell development so may be used to indicate developmental stage. Loss of surface expression indicates plasma cell differentiation.
• clonality malignant b-cells arise from a single parent cell so express light chain of a single type either kappa or lambda - light chain restriction . in almost all cases there will be some normal cells present so light chains usually are a mixture of kappa and lambda. however when there is a malignant clone either kappa or lambda begins to predominate. Studies most frequently suggest that if the kappa to lambda ratio is 3 1 or 3 1 then the presence of a clonal population can be inferred although correlation with other markers is needed.
• weak or absent light chain expression may be seen in DLBCL FL or CLL and more rarely in MCL or MZL. Overall around 10% of B-lymphoproliferative disorders do not express surface light chain.

summary tables

1. expression by acute leukaemias and by rare pro-b all poss early pre-b all poss pre-b all hi b all rare pro-t all rare mature-t all rare aml poss haemato-gones

• expressed by late haematogones

2. expression by b-lymphoproliferative disorders hi cll hi pll** hi mcl hi fl hi hcl** hi hclv l hi mzl hi lpl poss pcs