M. Abe et al., DIFFERENCES IN KAPPA TO LAMBDA (KAPPA LAMBDA) RATIOS OF SERUM AND URINARY FREE LIGHT-CHAINS/, Clinical and experimental immunology, 111(2), 1998, pp. 457-462
Free light chains (FLC) are a natural product of B lymphocytes and, as
such, represent a quantifiable biomarker of cellular proliferation. A
ccurate measurement of the concentrations of these components in serum
and urine provides a unique means of ascertaining B cell immunoglobul
in synthesis during physiologic and, especially, pathologic states, wh
ere such information has important diagnostic and therapeutic implicat
ions. Previously, use of such quantitative assays has been limited due
to the lack of potent serologic reagents specific for these component
s. We have immunized mice with kappa- and lambda-type monoclonal human
light chains (Fence Jones proteins (BJP)) and have obtained monoclona
l antibodies (MoAbs) that differentiate between unbound and bound ligh
t chains. These highly specific MoAbs were used to measure by ELISA th
e concentrations of FLC in the serum of 22 normal individuals and in u
rine from 16 of these subjects. The mean serum kappa and lambda FLC co
ncentrations were found to be 16.6 +/- 6.1 mu g/ml and 33.8 +/- 14.8 m
u g/ml, respectively. In contrast, the values for urinary kappa and la
mbda FLC were 2.96 +/- 1.84 mu g/ml and 1.07 +/- 0.69 mu g/ml, respect
ively. In each case studied, the serum kappa:lambda ratio was consiste
ntly less than that of urine (mean values, serum approximate to 1:2; u
rine approximate to 3:1). That the rate of synthesis of lambda-type FL
C exceeded that of kappa was evidenced in assays of culture fluid supe
rnatants of unstimulated normal peripheral blood mononuclear cells (PB
MC), where the mean kappa:lambda ratio was determined to be 1:1.4. Met
abolic studies in which mice were injected with pools of kappa- and la
mbda-type BJP prepared in ratios of 1:1, 1:2 and 1:4 demonstrated that
, regardless of the proportion, kappa FLC were preferentially excreted
. Our studies provide the first evidence that lambda FLC are secreted
by normal PBMC at a greater rate than are kappa FLC, as evidenced in b
iosynthetic studies and by measurement of their serum concentrations.
Further, we posit that quaternary structural differences between the t
wo light-chain isotypes may account for the predominance of kappa vers
us lambda components in urine.