B cells are involved in the adaptive immune system, producing specific antibodies to eliminate both exogenous and autologous antigens. This is achieved by generation of a diverse range of antigen receptors and selection of B cells expressing one type of immunoglobulin on its surface, acting as a B cell receptor (BCR) specific for a particular antigen (Zhang & Kipps, 2014). The likelihood of two different B cell clones having the same BCR is extremely low, however, similar or identical BCRs are seen expressed on cells obtained from different CLL patients (Zhang & Kipps, 2014).

Compared to normal B cells, CLL cells express IGHV1-69, IGHV4-34 and IGHV3-7 at increased rates and a restricted immunoglobulin gene repertoire indicates a role of common antigens in CLL B cell selection (Zhang & Kipps, 2014).

Antigens and selection of CLL B cells

Many CLL cells express immunoglobulins which recognise and bind myosin-exposed apoptotic cells (MEACs), reacting with non-muscle myosin heavy chain IIA (MYHIIA) (Zhang & Kipps, 2014; Chu et al., 2010). CLL cells with unmutated IGHVs more commonly bind MEACs than CLL cells with mutated IGHVs, suggesting that more than one antigen or epitope may be involved in driving the selection of CLL cells (Zhang & Kipps, 2014).

Microbial and viral antigens may be involved in the selection of CLL B cells, e.g. Ig encoded by IGHV1-69 can react with several gram-positive or gram-negative bacteria (Zhang & Kipps, 2014).